StemCell Therapy

Nanotechnology has many definitions but in general it is the use and application of materials with sizes in the nanometre range. Just as a millimetre is one-thousandth of a metre, a nanometre is one-millionth of a millimetre. In more understandable terms, a human hair is approximately 80,000 nanometres in diameter and the growing science and industry of nanotechnology utilises materials below 1000 nanometres. Benefits of working at this very small scale have been seen for many years over such diverse areas as electronics and energy storage to sunscreens and food packaging.

Nanomedicine is simply the application of nanotechnologies in a healthcare setting and the majority of benefits that have already been seen involve the use of nanoparticles to improve the behaviour of drug substances. Today, nanomedicines are used globally to improve the treatments and lives of patients suffering from a range of disorders including ovarian and breast cancer, kidney disease, fungal infections, elevated cholesterol, menopausal symptoms, multiple sclerosis, chronic pain, asthma and emphysema. The nanomedicines that are currently available are overcoming some of the difficulties experienced by normal medical approaches in delivering the benefit from the drug molecules used. In some cases the drugs have very little solubility in water and the human body struggles to absorb enough to treat the condition. In other cases, the drug molecule is absorbed well but the body removes the drug before it has had long enough to provide a benefit. Drugs may lead to side-effects due to poor delivery at the actual site of disease. For example, drugs that are targeting cancers must avoid healthy tissues and organs or damage can be caused. Nanomedicines therefore can play an important role in ensuring enough of the drug enters the body, that drug that does enter stays in the body for long periods and is targeted specifically to the areas that need treatment.

It has been known for many years that identifying illness or disease very early can help prevent long term damage or even death in patients. It is possible for many diseases that no symptoms are visible for many years but the human body does produce evidence of problems at the molecular level. Another important area of nanotechnology and nanomedicine is diagnostics. By studying and identifying individual molecules, it is possible to diagnose disease in time to improve the prognosis for the patient.

Over the coming years, the benefits of nanomedicines and new diagnostic tools will be felt by an increasing number of patients with considerable impact on global health.

This illustrative figure shows the different structures of nanomedicines and their approximate sizes. For comparison, the sizes of biological nanostructures are shown at the top of the figure.

Continue reading here:
what is nanomedicine The British Society for Nanomedicine

The translation of nanotechnology form the bench to the market imposed several challenges. General issues to consider during the development of nanomedicine products including physicochemical characterization, biocompatibility, and nanotoxicology evaluation, pharmacokinetics and pharmacodynamics assessment, process control, and scale-reproducibility (Figure ) are discussed in the sections that follow.

The characterization of a nanomedicine is necessary to understand its behavior in the human body, and to provide guidance for the process control and safety assessment. This characterization is not consensual in the number of parameters required for a correct and complete characterization. Internationally standardized methodologies and the use of reference nanomaterials are the key to harmonize all the different opinions about this topic (Lin et al., 2014; Zhao and Chen, 2016).

Ideally, the characterization of a nanomaterial should be carried out at different stages throughout its life cycle, from the design to the evaluation of its in vitro and in vivo performance. The interaction with the biological system or even the sample preparation or extraction procedures may modify some properties and interfere with some measurements. In addition, the determination of the in vivo and in vitro physicochemical properties is important for the understanding of the potential risk of nanomaterials (Lin et al., 2014; Zhao and Chen, 2016).

The Organization for Economic Co-operation and Development started a Working Party on Manufactured Nanomaterials with the International Organization for Standardization to provide scientific advice for the safety use of nanomaterials that include the respective physicochemical characterization and the metrology. However, there is not an effective list of minimum parameters. The following characteristics should be a starting point to the characterization: particle size, shape and size distribution, aggregation and agglomeration state, crystal structure, specific surface area, porosity, chemical composition, surface chemistry, charge, photocatalytic activity, zeta potential, water solubility, dissolution rate/kinetics, and dustiness (McCall et al., 2013; Lin et al., 2014).

Concerning the chemical composition, nanomaterials can be classified as organic, inorganic, crystalline or amorphous particles and can be organized as single particles, aggregates, agglomerate powders or dispersed in a matrix which give rise to suspensions, emulsions, nanolayers, or films (Luther, 2004).

Regarding dimension, if a nanomaterial has three dimensions below 100 nm, it can be for example a particle, a quantum dot or hollow sphere. If it has two dimensions below 100 nm it can be a tube, fiber or wire and if it has one dimension below 100 nm it can be a film, a coating or a multilayer (Luther, 2004).

Different techniques are available for the analysis of these parameters. They can be grouped in different categories, involving counting, ensemble, separation and integral methods, among others (Linsinger et al., 2012; Contado, 2015).

Counting methods make possible the individualization of the different particles that compose a nanomaterial, the measurement of their different sizes and visualization of their morphology. The particles visualization is preferentially performed using microscopy methods, which include several variations of these techniques. Transmission Electron Microscopy (TEM), High-Resolution TEM, Scanning Electron Microscopy (SEM), cryo-SEM, Atomic Force Microscopy and Particle Tracking Analysis are just some of the examples. The main disadvantage of these methods is the operation under high-vacuum, although recently with the development of cryo-SEM sample dehydration has been prevented under high-vacuum conditions (Linsinger et al., 2012; Contado, 2015; Hodoroaba and Mielke, 2015).

These methods involve two steps of sample treatment: the separation of the particles into a monodisperse fraction, followed by the detection of each fraction. Field-Flow Fractionation (FFF), Analytical Centrifugation (AC) and Differential Electrical Mobility Analysis are some of the techniques that can be applied. The FFF techniques include different methods which separate the particles according to the force field applied. AC separates the particles through centrifugal sedimentation (Linsinger et al., 2012; Contado, 2015; Hodoroaba and Mielke, 2015).

Ensemble methods allow the report of intensity-weighted particle sizes. The variation of the measured signal over time give the size distribution of the particles extracted from a combined signal. Dynamic Light Scattering (DLS), Small-angle X-ray Scattering (SAXS) and X-ray Diffraction (XRD) are some of the examples. DLS and QELS are based on the Brownian motion of the sample. XRD is a good technique to obtain information about the chemical composition, crystal structure and physical properties (Linsinger et al., 2012; Contado, 2015; Hodoroaba and Mielke, 2015).

The integral methods only measure an integral property of the particle and they are mostly used to determine the specific surface area. Brunauer Emmet Teller is the principal method used and is based on the adsorption of an inert gas on the surface of the nanomaterial (Linsinger et al., 2012; Contado, 2015; Hodoroaba and Mielke, 2015).

Other relevant technique is the electrophoretic light scattering (ELS) used to determine zeta potential, which is a parameter related to the overall charge a particle acquires in a particular medium. ELS measures the electrophoretic mobility of particles in dispersion, based on the principle of electrophoresis (Linsinger et al., 2012).

The Table shows some of principal methods for the characterization of the nanomaterials including the operational principle, physicochemical parameters analyzed and respective limitations.

Some of the principal methods for the characterization of the nanomaterials, operation principle, physicochemical parameters analyzed, and respective limitations (Luther, 2004; Linsinger et al., 2012; Lin et al., 2014; Contado, 2015; Hodoroaba and Mielke, 2015).

Another challenge in the pharmaceutical development is the control of the manufacturing process by the identification of the critical parameters and technologies required to analyse them (Gaspar, 2010; Gaspar et al., 2014; Sainz et al., 2015).

New approaches have arisen from the pharmaceutical innovation and the concern about the quality and safety of new medicines by regulatory agencies (Gaspar, 2010; Gaspar et al., 2014; Sainz et al., 2015).

Quality-by-Design (QbD), supported by Process Analytical Technologies (PAT) is one of the pharmaceutical development approaches that were recognized for the systematic evaluation and control of nanomedicines (FDA, 2004; Gaspar, 2010; Gaspar et al., 2014; Sainz et al., 2015; European Medicines Agency, 2017).

Note that some of the physicochemical characteristics of nanomaterials can change during the manufacturing process, which compromises the quality and safety of the final nanomedicine. The basis of QbD relies on the identification of the Quality Attributes (QA), which refers to the chemical, physical or biological properties or another relevant characteristic of the nanomaterial. Some of them may be modified by the manufacturing and should be within a specific range for quality control purposes. In this situation, these characteristics are considered Critical Quality Attributes (CQA). The variability of the CQA can be caused by the critical material attributes and process parameters (Verma et al., 2009; Riley and Li, 2011; Bastogne, 2017; European Medicines Agency, 2017).

The quality should not be tested in nanomedicine, but built on it instead, by the understanding of the therapeutic purpose, pharmacological, pharmacokinetic, toxicological, chemical and physical properties of the medicine, process formulation, packaging, and the design of the manufacturing process. This new approach allows better focus on the relevant relationships between the characteristics, parameters of the formulation and process in order to develop effective processes to ensure the quality of the nanomedicines (FDA, 2014).

According to the FDA definition PAT is a system for designing, analzsing, and controlling manufacturing through timely measurements (i.e., during processing) of critical quality and performance attributes of raw and in-process materials and processes, with the goal of ensuring final product quality (FDA, 2014). The PAT tools analyse the critical quality and performance attributes. The main point of the PAT is to assure and enhance the understanding of the manufacturing concept (Verma et al., 2009; Riley and Li, 2011; FDA, 2014; Bastogne, 2017; European Medicines Agency, 2017).

Biocompatibility is another essential property in the design of drug delivery systems. One very general and brief definition of a biocompatible surface is that it cannot trigger an undesired' response from the organism. Biocompatibility is alternatively defined as the ability of a material to perform with an appropriate response in a specific application (Williams, 2003; Keck and Mller, 2013).

Pre-clinical assessment of nanomaterials involve a thorough biocompatibility testing program, which typically comprises in vivo studies complemented by selected in vitro assays to prove safety. If the biocompatibility of nanomaterials cannot be warranted, potentially advantageous properties of nanosystems may raise toxicological concerns.

Regulatory agencies, pharmaceutical industry, government, and academia are making efforts to accomplish specific and appropriate guidelines for risk assessment of nanomaterials (Hussain et al., 2015).

In spite of efforts to harmonize the procedures for safety evaluation, nanoscale materials are still mostly treated as conventional chemicals, thus lacking clear specific guidelines for establishing regulations and appropriate standard protocols. However, several initiatives, including scientific opinions, guidelines and specific European regulations and OECD guidelines such as those for cosmetics, food contact materials, medical devices, FDA regulations, as well as European Commission scientific projects (NanoTEST project, http://www.nanotest-fp7.eu) specifically address nanomaterials safety (Juillerat-Jeanneret et al., 2015).

In this context, it is important to identify the properties, to understand the mechanisms by which nanomaterials interact with living systems and thus to understand exposure, hazards and their possible risks.

Note that the pharmacokinetics and distribution of nanoparticles in the body depends on their surface physicochemical characteristics, shape and size. For example, nanoparticles with 10 nm in size were preferentially found in blood, liver, spleen, kidney, testis, thymus, heart, lung, and brain, while larger particles are detected only in spleen, liver, and blood (De Jong et al., 2008; Adabi et al., 2017).

In turn, the surface of nanoparticles also impacts upon their distribution in these organs, since their combination with serum proteins available in systemic circulation, influencing their cellular uptake. It should be recalled that a biocompatible material generates no immune response. One of the cause for an immune response can rely on the adsorption pattern of body proteins. An assessment of the in vivo protein profile is therefore crucial to address these interactions and to establish biocompatibility (Keck et al., 2013).

Finally, the clearance of nanoparticles is also size and surface dependent. Small nanoparticles, bellow 2030 nm, are rapidly cleared by renal excretion, while 200 nm or larger particles are more efficiently taken up by mononuclear phagocytic system (reticuloendothelial system) located in the liver, spleen, and bone marrow (Moghimi et al., 2001; Adabi et al., 2017).

Studies are required to address how nanomaterials penetrate cells and tissues, and the respective biodistribution, degradation, and excretion.

Due to all these issues, a new field in toxicology termed nanotoxicology has emerged, which aims at studying the nanomaterial effects deriving from their interaction with biological systems (Donaldson et al., 2004; Oberdrster, 2010; Fadeel, 2013).

The evaluation of possible toxic effects of the nanomaterials can be ascribed to the presence of well-known molecular responses in the cell. Nanomaterials are able to disrupt the balance of the redox systems and, consequently, lead to the production of reactive species of oxygen (ROS). ROS comprise hydroxyl radicals, superoxide anion and hydrogen peroxide. Under normal conditions, the cells produce these reactive species as a result of the metabolism. However, when exposed to nanomaterials the production of ROS increases. Cells have the capacity to defend itself through reduced glutathione, superoxide dismutase, glutathione peroxidase and catalase mechanisms. The superoxide dismutase converts superoxide anion into hydrogen peroxide and catalase, in contrast, converts it into water and molecular oxygen (Nel et al., 2006; Arora et al., 2012; Azhdarzadeh et al., 2015). Glutathione peroxidase uses glutathione to reduce some of the hydroperoxides. Under normal conditions, the glutathione is almost totally reduced. Nevertheless, an increase in ROS lead to the depletion of the glutathione and the capacity to neutralize the free radicals is decreased. The free radicals will induce oxidative stress and interact with the fatty acids in the membranes of the cell (Nel et al., 2006; Arora et al., 2012; Azhdarzadeh et al., 2015).

Consequently, the viability of the cell will be compromised by the disruption of cell membranes, inflammation responses caused by the upregulation of transcription factors like the nuclear factor kappa , activator protein, extracellular signal regulated kinases c-Jun, N-terminal kinases and others. All these biological responses can result on cell apoptosis or necrosis. Distinct physiological outcomes are possible due to the different pathways for cell injury after the interaction between nanomaterials and cells and tissues (Nel et al., 2006; Arora et al., 2012; Azhdarzadeh et al., 2015).

Over the last years, the number of scientific publications regarding toxicological effects of nanomaterials have increased exponentially. However, there is a big concern about the results of the experiments, because they were not performed following standard and harmonized protocols. The nanomaterial characterization can be considered weak once there are not standard nanomaterials to use as reference and the doses used in the experiences sometimes cannot be applied in the biological system. Therefore, the results are not comparable. For a correct comparison, it is necessary to perform a precise and thorough physicochemical characterization to define risk assessment guidelines. This is the first step for the comparison between data from biological and toxicological experiments (Warheit, 2008; Fadeel et al., 2015; Costa and Fadeel, 2016).

Although nanomaterials may have an identical composition, slight differences e.g., in the surface charge, size, or shape could impact on their respective activity and, consequently, on their cellular fate and accumulation in the human body, leading to different biological responses (Sayes and Warheit, 2009).

Sayes and Warheit (2009) proposed a three phases model for a comprehensive characterization of nanomaterials. Accordingly, the primary phase is achieved in the native state of the nanomaterial, specifically, in its dry state. The secondary characterization is performed with the nanomaterials in the wet phase, e.g., as solution or suspension. The tertiary characterization includes in vitro and in vivo interactions with biological systems. The tertiary characterization is the most difficult from the technical point of view, especially in vivo, because of all the ethical questions concerning the use of animals in experiments (Sayes and Warheit, 2009).

Traditional toxicology uses of animals to conduct tests. These types of experiments using nanomaterials can be considered impracticable and unethical. In addition, it is time-consuming, expensive and sometimes the end points achieved are not enough to correctly correlate with what happens in the biological systems of animals and the translation to the human body (Collins et al., 2017).

In vitro studies are the first assays used for the evaluation of cytotoxicity. This approach usually uses cell lines, primary cells from the tissues, and/or a mixture of different cells in a culture to assess the toxicity of the nanomaterials. Different in vitro cytotoxicity assays to the analysis of the cell viability, stress, and inflammatory responses are available. There are several cellular processes to determine the cell viability, which consequently results in different assays with distinct endpoints. The evaluation of mitochondrial activity, the lactate dehydrogenase release from the cytosol by tretazolium salts and the detection of the biological marker Caspase-3 are some of the examples that imposes experimental variability in this analysis. The stress response is another example which can be analyzed by probes in the evaluation of the inflammatory response via enzyme linked immunosorbent assay are used (Kroll et al., 2009).

As a first approach, in vitro assays can predict the interaction of the nanomaterials with the body. However, the human body possesses compensation mechanisms when exposed to toxics and a huge disadvantage of this model is not to considered them. Moreover, they are less time consuming, more cost-effective, simpler and provide an easier control of the experimental conditions (Kroll et al., 2009; Fadeel et al., 2013b).

Their main drawback is the difficulty to reproduce all the complex interactions in the human body between sub-cellular levels, cells, organs, tissues and membranes. They use specific cells to achieve specific endpoints. In addition, in vitro assays cannot predict the physiopathological response of the human body when exposed to nanomaterials (Kroll et al., 2009; Fadeel et al., 2013b).

Another issue regarding the use of this approach is the possibility of interaction between nanomaterials and the reagents of the assay. It is likely that the reagents used in the in vitro assays interfere with the nanomaterial properties. High adsorption capacity, optical and magnetic properties, catalytic activity, dissolution, and acidity or alkalinity of the nanomaterials are some of the examples of properties that may promote this interaction (Kroll et al., 2009).

Many questions have been raised by the regulators related to the lack of consistency of the data produced by cytotoxicity assays. New assays for a correct evaluation of the nanomaterial toxicity are, thus, needed. In this context, new approaches have arisen, such as the in silico nanotoxicology approach. In silico methods are the combination of toxicology with computational tools and bio-statistical methods for the evaluation and prediction of toxicity. By using computational tools is possible to analyse more nanomaterials, combine different endpoints and pathways of nanotoxicity, being less time-consuming and avoiding all the ethical questions (Warheit, 2008; Raunio, 2011).

Quantitative structure-activity relationship models (QSAR) were one the first applications of computational tools applied in toxicology. QSAR models are based on the hypothesis that the toxicity of nanomaterials and their cellular fate in the body can be predicted by their characteristics, and different biological reactions are the result of physicochemical characteristics, such as size, shape, zeta potential, or surface charge, etc., gathered as a set of descriptors. QSAR aims at identifying the physicochemical characteristics which lead to toxicity, so as to provide alterations to reduce toxicology. A mathematical model is created, which allows liking descriptors and the biological activity (Rusyn and Daston, 2010; Winkler et al., 2013; Oksel et al., 2015).

Currently, toxigenomics is a new area of nanotoxicology, which includes a combination between genomics and nanotoxicology to find alterations in the gene, protein and in the expressions of metabolites (Rusyn et al., 2012; Fadeel et al., 2013a).

Hitherto, different risk assessment approaches have been reported. One of them is the DF4nanoGrouping framework, which concerns a functionality driven scheme for grouping nanomaterials based on their intrinsic properties, system dependent properties and toxicological effects (Arts et al., 2014, 2016). Accordingly, nanomaterials are categorized in four groups, including possible subgroups. The four main groups encompass (1) soluble, (2) biopersistent high aspect ratio, (3) passive, that is, nanomaterials without obvious biological effects and (4) active nanomaterials, that is, those demonstrating surface-related specific toxic properties. The DF4nanoGrouping foresees a stepwise evaluation of nanomaterial properties and effects with increasing biological complexity. In case studies that includes carbonaceous nanomaterials, metal oxide, and metal sulfate nanomaterials, amorphous silica and organic pigments (all nanomaterials having primary particle sizes smaller than 100 nm), the usefulness of the DF4nanoGrouping for nanomaterial hazard assessment has already been established. It facilitates grouping and targeted testing of nanomaterials, also ensuring that enough data for the risk assessment of a nanomaterial are available, and fostering the use of non-animal methods (Landsiedel et al., 2017). More recently, DF4nanoGrouping developed three structure-activity relationship classification, decision tree, models by identifying structural features of nanomaterials mainly responsible for the surface activity (size, specific surface area, and the quantum-mechanical calculated property lowest unoccupied molecular orbital), based on a reduced number of descriptors: one for intrinsic oxidative potential, two for protein carbonylation, and three for no observed adverse effect concentration (Gajewicz et al., 2018)

Keck and Mller also proposed a nanotoxicological classification system (NCS) (Figure ) that ranks the nanomaterials into four classes according to the respective size and biodegradability (Mller et al., 2011; Keck and Mller, 2013).

Nanotoxicological classification (reproduced with permission from Keck and Mller, 2013).

Due to the size effects, this parameter is assumed as truly necessary, because when nanomaterials are getting smaller and smaller there is an increase in solubility, which is more evident in poorly soluble nanomaterials than in soluble ones. The adherence to the surface of membranes increases with the decrease of the size. Another important aspect related to size that must be considered is the phagocytosis by macrophages. Above 100 nm, nanomaterials can only be internalized by macrophages, a specific cell population, while nanomaterials below 100 nm can be internalized by any cell due to endocytosis. Thus, nanomaterials below 100 nm are associated to higher toxicity risks in comparison with nanomaterials above 100 nm (Mller et al., 2011; Keck and Mller, 2013).

In turn, biodegradability was considered a required parameter in almost all pharmaceutical formulations. The term biodegradability applies to the biodegradable nature of the nanomaterial in the human body. Biodegradable nanomaterials will be eliminated from the human body. Even if they cause some inflammation or irritation the immune system will return to the regular function after elimination. Conversely, non-biodegradable nanomaterials will stay forever in the body and change the normal function of the immune system (Mller et al., 2011; Keck and Mller, 2013).

There are two more factors that must be taken into account in addition to the NCS, namely the route of administration and the biocompatibility surface. When a particle is classified by the NCS, toxicity depends on the route of administration. For example, the same nanomaterials applied dermally or intravenously can pose different risks to the immune system.

In turn, a non-biocompatibility surface (NB) can activate the immune system by adsorption to proteins like opsonins, even if the particle belongs to the class I of the NCS (Figure ). The biocompatibility (B) is dictated by the physicochemical surface properties, irrespective of the size and/or biodegradability. This can lead to further subdivision in eight classes from I-B, I-NB, to IV-B and IV-NB (Mller et al., 2011; Keck and Mller, 2013).

NCS is a simple guide to the evaluation of the risk of nanoparticles, but there are many other parameters playing a relevant role in nanotoxicity determination (Mller et al., 2011; Keck and Mller, 2013). Other suggestions encompass more general approaches, combining elements of toxicology, risk assessment modeling, and tools developed in the field of multicriteria decision analysis (Rycroft et al., 2018).

Read the rest here:
Nanomedicine: Principles, Properties, and Regulatory Issues

The Johns Hopkins Center for Nanomedicine (CNM) brings together engineers, scientists, and clinicians working together under one roof on translation of novel drug and gene delivery technologies. The focus is to overcome major challenges to drug efficacy, including biological barriers to delivery, patient compliance, and toxicity. Furthermore, we educate and train the next generation of researchers to innovate at the interface of engineering, medicine, and the life sciences in the development of drug delivery technologies with potential for clinical implementation. We believe that collaboration and commitment to diversity are key in having the maximum impact on human health.

Nanomedicine is defined as the medical application of nanotechnology. In the CNM, we focus on harnessing nanotechnology to more effectively diagnose, treat, and prevent various diseases. Our entire bodies are exposed to the medicines that we take, which can lead to unpleasant side effects and minimize the amount of medicine that reaches the places where it is needed. Medications can be more efficiently delivered to the site of action using nanotechnology, resulting in improved outcomes with less medication.

We design our nanotechnology-based platforms for clinical translation. What this means is that we strive for innovative simplicity and the use of components that have a history of medical safety, so that our nanomedicines can be tested in clinical trials and developed into useful products. To this end, we often design our platforms to mimic nature or select our systems based on how they naturally distribute in the body. To date, our faculty have founded more than 10 start-up companies, resulting in several FDA-approved products and others being tested in clinical trials.

Focus areas: Glaucoma, age-related macular degeneration, diabetic retinopathy, retinitis pigmentosa, diabetic macular edema, uveitis, dry eye disease, corneal neovascularization, corneal graft rejection, thyroid eye disease, cataract surgery, glaucoma surgery, ocular trauma

Focus areas:Immunotherapy, cancers of the pancreas, cervix, ovary, lung, brain, bladder, and colorectum

Focus areas: COVID-19, inflammatory bowel disease, pancreatitis, liver cirrhosis, various cancers, intrauterine inflammation, atherosclerosis, arthritis

Focus areas: Cystic fibrosis, asthma, chronic obstructive pulmonary disease, lung cancer

Focus areas: Preterm birth, intrauterine inflammation, infections,in vitrofertilization, reproductive tract cancers, contraception

Focus areas:Brain tumors, cerebral palsy, neonatal stroke, traumatic brain injury, autism spectrum disorders, Parkinsons disease, Alzheimers disease

The CNM team includes basic science and clinical faculty, research staff, postdoctoral fellows, graduate students, and undergraduates. Our goal is to train, mentor, and promote inclusive and supportive research environments.

In addition to a rigorous and broad training in unbiased experimental design, methods, data analysis, interpretation, and reporting, we strive to support our trainees in career and professional development. We proudly support diverse career goals, and our alumni have gone on to careers in academia, industry, regulatory, venture capital, consulting, science communication, policy, law, and medicine. We participate in numerous training programs that promote and develop trainees from low income and underrepresented groups in biomedical research.

Kannan Lab

Research Specialist, Ensign Lab

Research Specialist, Ensign Lab

Research Specialist, Ensign Lab

Research Specialist

Lab Manager

Research Technologist

Lab Manager

Research Engineer

Hanes Lab

Ensign Lab

Mahdi Forouharshad, Ph.D.

Thanuia Marasarakottige Yogananda, Ph.D.

Balachandra Chenikkayala, Ph.D.

Durgadas Cherukaraveedu, Ph.D.

Ensign Lab

Hanes Lab

Ensign Lab

Ensign Lab

Ensign Lab

Hanes Lab

See More

Read the rest here:
Center for Nanomedicine - Johns Hopkins Medicine

J Control Release. 2020 Oct 10; 326: 164171.

aCuradigm SAS, 60 rue de wattignies, 75012 Paris, France

bDepartment of Biotechnology and Nanomedicine, SINTEF Industry, 7465 Trondheim, Norway

cLIFNano Therapeutics, 10 Fendon Road, University of Cambridge Clinical School, Cambridge CB1 7RT, UK

dNanotech Lab, Te.Far.T.I., Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 103, 41124 Modena, Italy

eGesellschaft fuer Bioanalytik Muenster e.V., Mendelstrasse 17, 48151 Muenster, Germany

bDepartment of Biotechnology and Nanomedicine, SINTEF Industry, 7465 Trondheim, Norway

fETPN association, 64-66 rue des archives, 75003 Paris, France

gDepartment of Clinical Chemistry and Haematology, University Medical Centre Utrecht, 3584, CX, Utrecht, the Netherlands

fETPN association, 64-66 rue des archives, 75003 Paris, France

bDepartment of Biotechnology and Nanomedicine, SINTEF Industry, 7465 Trondheim, Norway

aCuradigm SAS, 60 rue de wattignies, 75012 Paris, France

bDepartment of Biotechnology and Nanomedicine, SINTEF Industry, 7465 Trondheim, Norway

cLIFNano Therapeutics, 10 Fendon Road, University of Cambridge Clinical School, Cambridge CB1 7RT, UK

dNanotech Lab, Te.Far.T.I., Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 103, 41124 Modena, Italy

eGesellschaft fuer Bioanalytik Muenster e.V., Mendelstrasse 17, 48151 Muenster, Germany

fETPN association, 64-66 rue des archives, 75003 Paris, France

gDepartment of Clinical Chemistry and Haematology, University Medical Centre Utrecht, 3584, CX, Utrecht, the Netherlands

Corresponding author at: Curadigm SAS, 60 rue de wattignies, 75012 Paris, France.

1These authors contributed equally.

Received 2020 Apr 9; Revised 2020 Jul 6; Accepted 2020 Jul 7.

Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

The situation of the COVID-19 pandemic reminds us that we permanently need high-value flexible solutions to urgent clinical needs including simplified diagnostic technologies suitable for use in the field and for delivering targeted therapeutics. From our perspective nanotechnology is revealed as a vital resource for this, as a generic platform of technical solutions to tackle complex medical challenges. It is towards this perspective and focusing on nanomedicine that we take issue with Prof Park's recent editorial published in the Journal of Controlled Release. Prof. Park argued that in the last 15years nanomedicine failed to deliver the promised innovative clinical solutions to the patients (Park, K. The beginning of the end of the nanomedicine hype. Journal of Controlled Release, 2019; 305, 221222 [1]. We, the ETPN (European Technology Platform on Nanomedicine) [2], respectfully disagree. In fact, the more than 50 formulations currently in the market, and the recent approval of 3 key nanomedicine products (e. g. Onpattro, Hensify and Vyxeos), have demonstrated that the nanomedicine field is concretely able to design products that overcome critical barriers in conventional medicine in a unique manner, but also to deliver within the cells new drug-free therapeutic effects by using pure physical modes of action, and therefore make a difference in patients lives. Furthermore, the >400 nanomedicine formulations currently in clinical trials are expecting to bring novel clinical solutions (e.g. platforms for nucleic acid delivery), alone or in combination with other key enabling technologies to the market, including biotechnologies, microfluidics, advanced materials, biomaterials, smart systems, photonics, robotics, textiles, Big Data and ICT (information & communication technologies) more generally. However, we agree with Prof. Park that it is time to examine the sources of difficulty in clinical translation of nanomedicine and move forward . But for reaching this goal, the investments to support clinical translation of promising nanomedicine formulations should increase, not decrease. As recently encouraged by EMA in its roadmap to 2025, we should create more unity through a common knowledge hub linking academia, industry, healthcare providers and hopefully policy makers to reduce the current fragmentation of the standardization and regulatory body landscape. We should also promote a strategy of cross-technology innovation, support nanomedicine development as a high value and low-cost solution to answer unmet medical needs and help the most promising innovative projects of the field to get better and faster to the clinic. This global vision is the one that the ETPN chose to encourage for the last fifteen years. All actions should be taken with a clear clinical view in mind, without any fanfare, to focus on what matters in real life, which is the patient and his/her quality of life.

This ETPN overview of achievements in nanomedicine serves to reinforce our drive towards further expanding and growing the maturity of nanomedicine for global healthcare, accelerating the pace of transformation of its great potential into tangible medical breakthroughs.

Keywords: Nanomedicine, Clinical translation, Nanotechnology, Healthtech, Regulatory, Standardization

Nanomedicine unquestionably makes a difference for patients.

Innovative nanomedicines open perspectives to make a difference outside oncology.

High need for a harmonized international regulatory framework for nanomedicines.

Nanomedicine is a cross-sectorial and cross-technological solution for healthcare.

For decades the field of nanomedicine has promised to revolutionize treatment outcomes for millions of patients. Has nanomedicine succeeded in meeting the initial expectations, making a real difference for patients or is it still only delivering lofty promises of what we hope it might do someday? In his editorial in the Journal of Controlled Release [1], Prof. Park argues that the field of nanomedicine has been clearly overrated, that it was overly focused on cancer therapy and that its promises probably never will be realized. Based on these conclusions, he suggests that the massive resources, time and financial investments allocated to the field of nanomedicine should be refocused on other priorities. It may be true that the publicly funded research investment in the field is decreasing. For example, the US National Cancer Institute (NCI) recently announced that, after 15years, it will stop funding the Centers of Cancer Nanotechnology Excellence (CCNEs). But the reason for setting aside this funding mechanism was not the failure of the nanomedicine field. On the contrary, the program was supposed to only support emerging technologies, while nanomedicine is now considered resilient enough to compete in other standard funding mechanisms. Moreover, Prof. Grodzinski in response to Park, pointed out that the CCNEs program was very successful, not only producing >3400 nanomedicine publications, but also generating concrete results, such as the creation of >100 start-up companies, and products entering >30 clinical trials in the US [3]. The Nanomedicine and Nanoscale Delivery (NND) focus group of the Controlled Release Society (CRS) also recently joined the discussion, arguing in favor of the solid progresses made by nanomedicine [4].

The debate is open: are we at the beginning of the end of the nanomedicine hype, as suggested by Prof. Park, or are we just at the end of the beginning which will guide nanomedicine into a new, more mature phase? To answer this question, we propose to first proceed as described in the citation used by Prof. Park himself: Innovators who seek to revolutionize and disrupt an industry must tell investors the truth about what their technology can do today, not just what they hope it might do someday. We will argue in section one, how, in our opinion, nanomedicine has already made a concrete difference in the treatment of cancer and of other diseases. Then, in section two we will discuss the bottlenecks that are still delaying nanomedicine's efficient translation into the clinic, we will describe the main on-going European and international initiatives to sustain the field alone or in combination with other key enabling technologies (KETs). Finally, we will conclude on the potential role that European infrastructures may play in the future, notably within the framework of the upcoming Work Programme Horizon Europe led by the European Commission (E.C.).

It is very often claimed that nanomedicine failed to meet the initial expectations in drug delivery, since less than 1% of the active pharmacological ingredient (API) is locally released, e.g. in cancer treatment in the tumoral tissues [5,6]. As pointed out by Scott Mc-Neil, former Director of the Nanotechnology Characterization Laboratory (NCL) of the NCI, the average amount of the API delivered locally may not be the only parameter to judge the success of nanomedicine in cancer therapy, since other pharmacological parameters, as peak drug concentration, clearance rate and half time elimination may be significantly improved, increasing the therapeutic outcome and also reducing side effects [7]. More importantly, the nanomedicine success cannot be judged only by considering the delivered dose, since nanoparticles are not acting only as passive drug carriers. In the last three years, three new formulations were approved, Vyxeos, Onpattro and Hensify, clearly demonstrating that a new generation of nanomedicine formulations has successfully reached the market, opening new clinical perspectives based on their unique physico-chemical properties.

Currently more than 50 nanomedicine formulations have been approved for clinical use, as recently reviewed by multiple authors [[8], [9], [10]]. These marketed nanomedicine formulations are approved for cancer treatment, iron-replacement therapies, anesthetics, fungal treatments, macular degeneration, and for the treatment of genetic rare diseases [8]. Nano/microparticle imaging agents have also been included in the statistics. The majority of approved NP classes are represented by liposomes, iron colloids, protein-based NP, nano-emulsions, nanocrystals and metal oxide nanoparticles. The three new formulations mentioned in the previous section, not only show that the number of formulations approved are steadily increasing (), but that new generations of nanomedicine are now reaching the market.

Evolution of the approved nanomedicine formulations (cumulative number/year). First year of approval reported for formulations approved by multiple agencies (e.g. EMA and FDA).

Vyxeos was approved in 2017 by the FDA for the treatment of acute myeloid leukemia [11]. It allows the simultaneous delivery of two drugs, cytarabine and daunorubicin, at a synergic fixed 5:1 ratio to increase treatment efficacy with a lower cumulated dose. Due to differential pharmacodynamics and biodistribution of drugs, a temporal and spatial controlled delivery of this optimal ratio cannot be reached by any other approach than by the encapsulation of the chosen mix of drugs in a nano-object. It is easy to envision that such a success will be reproduced with various drug combinations.

In 2018 Onpattro, the first lipid-based nanoformulation encapsulating siRNA, was approved for the treatment of transthyretin amyloidosis [12], a rare disease. This approval is a great achievement, nanomedicine being the first technology platform answering the needs of nucleic acid delivery and finally making it available for patients. Indeed, nucleotide-based drugs have an enormous therapeutic potential but pose specific delivery challenges. In fact, nucleotides are rapidly degraded in vivo and have little or no possibility to reach the target region. Furthermore, they are negatively charged and uptake into cells is electrostatically hindered. Hence, nucleotide drugs need both protection and a trojan horse to enter cells. The design of Onpattro combines an efficient encapsulation of siRNA with prevention of its degradation in vivo but also with the ability to perform endosomal escape and delivery of siRNA within the cell cytoplasm. Considering the high number of ongoing clinical trials based on nanomedicines encapsulating nucleic acids, including mRNAs, several new products will be expected to reach the market in the near future. The current global Covid-19 pandemic highlights that a vaccine, based on mRNA encapsulation in lipid-based nanoparticles, could now be developed with unprecedented speed. Importantly, the therapeutic potential of mRNA is vastly larger, and can provide solutions in multiple areas including cancer vaccines and immune activation, in-body production of patients' own therapeutic antibodies, protein replacement therapies and regenerative medicine. Importantly, delivery of nucleic acids could be used for any kind of permanent gene therapy of, conceivably, any genetic disorder by encoding of the CRISPR/Cas9 complex [13]. Therefore, we believe that Onpattro is only the very beginning of a paradigm shift in the treatment of various therapeutic areas including oncology, but also rare diseases, genetic or infectious diseases.

Nanomedicine cannot be considered simply as a drug delivery system anymore since nanomaterials themselves may become the active therapeutic ingredient. Nowadays, radiotherapy's efficacy is limited by the tolerance of normal tissues adjacent to the tumor which reduces the energy dose that can be administered safely the patient. Nanotechnologies have created a new profile of material interactions with cell biology. The use of a new class of radiation-enhancing nanoparticles could be a breakthrough approach for the local treatment of solid tumors that are treated with radiotherapy. NBTXR3 is a first-in-class nanoparticle composed of functionalized crystalline hafnium oxide (HfO2). NBTXR3 nanoparticles were chosen for clinical development because of their excellent ratio for x-ray absorption and acceptable safety. Once activated by ionizing radiation, NBTXR3 administered intratumorally yields a cell-localized high energy deposit and increased cell death compared with the same dose of radiation alone, without adding toxicity to the surrounding tissues. This innovative approach proposes to broaden the therapeutic window of radiation therapy by opening the possibility to bring physics at the heart of the cells without changing radiotherapy practice. NBTXR3 obtained its CE mark for the treatment of locally advanced soft tissue sarcoma in 2019 and the results from its phase 23 clinical trial were recently published [14].

Other examples of the difference made by nanomedicine can be found in liposomal marketed products in various therapeutic areas [15]. The final aim of this paper is not to provide an exhaustive list of products, but rather to highlight and focus on some of them, e.g. Visudyne, a liposomal formulation of verteporin, used in the treatment of age-related macular degeneration (AMD) by photodynamic therapy [16]. Encapsulation of verteporin is required since this molecule undergoes self-aggregation in aqueous medium, limiting its bioavailability. Ocular delivery is very challenging due to the presence of biological barriers (cornea, aqueous humor, etc.) which reduce the bioavailability of topically or intraocularly administered therapeutic agents. This situation demands frequent therapeutic agent administration which could limit the treatment especially for invasive intra-ocular administration which can cause intraocular bleeding associated with pain and discomfort that results in poor patient compliance. This demonstrates that nanomedicine has also made a difference in this therapeutic area by offering the possibility to improve therapeutic agents' bioavailability for intraocularly and topically administered drugs and sustained drug release which reduces the frequency of drug administrations. Such benefits explain why there are already 10 nanomedicine-based products marketed for ocular treatment [17].

Imaging also benefits from nanomedicine's properties. For example, Magtrace is made of magnetic iron nanoparticles enable tracing of the sentinel node in breast cancer without the use of radiomarkers, resulting in a more efficient biopsy and detection of cancer cell migration [18].

By analyzing the active or recruiting clinical trials in the clinicaltrials.gov database we were able to identify 409 clinical trials focusing on therapy and diagnostics involving nanomedicines. From the beginning of 2018, more than 247 new clinical trials (active or recruiting) have been started. Interestingly, in May 2020 at least 3 trials were already started on vaccines for COVID-19 based on lipid-based nanoparticles and this number will probably increase significantly in the upcoming months. The most common formulations under investigation are still liposomes and protein based-nanoparticles, e.g. Nab-paclitaxel/Abraxane, but since 2015 the number of other types of nanomedicines reaching clinical testing has drastically increased with new innovative concepts such as lipid-based nanoparticles for nucleic acid delivery or metal oxides as radio-enhancers. Multiple trials are also ongoing on polymeric nanoparticles, virus like particles, and micelles, as represented in .

Nanoparticle classes investigated in ongoing clinical trials. The analysis was performed on 409 clinical trials from 2008 to 2020 (active, ongoing or recruiting), identified in the clinicaltrials.gov database in May 2020. Search limited to trials identified with the following keywords: nanoparticle, liposome, liposomal, lipid, vaccine, micelle, nanocrystal, virus like particle, silica particle, iron oxide, extracellular vesicle, dendrimer, nanobubble, lipoplex, gold nanoparticle. These keywords were used alone or in association with other diseases or technologies specific keywords: COVID-19, mRNA, nucleic acid, cancer. Only trials using nanoparticles were selected, eliminating doubloons arising from multiple searches. Repartition of nanoparticle types is presented for all ongoing clinical trials, for cancer related applications (65% of the total) and for all applications outside oncology (35% of the total). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Even if nanomedicine is still highly focused on oncology, there is a clear shift towards other clinical applications: while clinical trials for cancer treatments remain above 50%, the number of clinical trials is increasing in other indications including pain treatment, infection, and vaccination. Furthermore, new indications/areas for treatment are emerging encompassing diseases related to neural system diseases, eye diseases and genetic diseases ().

Categorization of clinical trials based on nanomedicine formulation per indication: A) analysis on all the 409 trials and b) repartition per year in the 2016- May 2020 period (333 trials). The analysis was performed on 409 clinical trials (active, ongoing or recruiting), identified in the clinicaltrials.gov database in May 2020. Search limited to trials identified with the following keywords: nanoparticle, liposome, liposomal, lipid, vaccine, micelle, nanocrystal, virus like particle, silica particle, iron oxide nanoparticle, extracellular vesicle, dendrimer, nanobubble, lipoplex, gold nanoparticle. These keywords were used alone or in association with other diseases or technologies specific keywords: COVID-19, mRNA, nucleic acid, cancer. Only trials using nanoparticles were selected, eliminating doubloons arising from multiple searches. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

65% of currently ongoing clinical trials are focused on cancer applications. To beat cancer, nanomedicine can offer great contributions for better treatments and early diagnosis. It is important to stress that even if the main goal remains to reduce or eradicate cancer, it is equally important to improve the quality of life of patients during treatment, helping to reduce the, often devastating, side effects. This is also where nanomedicine can significantly contribute. Nanomaterial's potential to deliver drugs locally, ensuring the therapeutic outcome by also reducing side effects is thus very important in cancer applications [5]. In this perspective, anti-cancer vaccines and personalized immuno-therapy (nucleic acids-based technologies) can notably be developed by nucleic acids-based technologies encapsulated in nanoparticle drug delivery systems. Multiple clinical trials are currently ongoing on lipid-based nanoparticles and on lipoplexes. Radio-enhancers like NBTXR3, could be a revolutionary concept for treating solid tumors, by locally enhancing the delivered dose of radiation. Stimuli-responsive nano-carriers with hyperthermia, are another innovative concept explored in clinical trials with the same purpose. For example, Thermodox, a heat sensitive liposome loaded with doxorubicin [19], is under clinical investigation in the OPTIMA Phase III Study for Primary Liver Cancer in combination with hyperthermia. In this clinical application, the combination of a stimuli-responsive nano-carrier with hyperthermia treatment, would allow a better temporal and spatial control of drug release, improving the therapeutic outcome with a lower dose.

Nanomedicine can also support early cancer diagnosis by providing ultrasensitive contrast agents. Several examples of nano-sized systems for diagnostic are currently investigated in clinical trials, including iron oxide nanoparticles for PET/MRI, and liposome/nanoparticle [18] mediated delivery of contrast agents (99Tc or 111In as examples) to be used in scintigraphy, SPECT or PET analysis.

Among the trials identified, 35% are investigating the use of nanomedicine for other clinical applications than cancer, demonstrating that nanomedicine could make a difference in other therapeutic areas, such as the central nervous system (CNS). Based on their unique physico-chemical properties (e. g. size, targeting agent coupling), nanomedicines are able to act on / pass through the blood brain barrier (BBB) and deliver the treatment more efficiently within the CNS. Tailored nanomedicines can pass through the BBB via transcytosis or endocytosis. Relevant preclinical results were obtained in various animal models of brain diseases as gliomas [20], Huntington's [21], Alzheimer's [[22], [23], [24]] or neurometabolic diseases [[25], [26], [27]]. Strategies based on transcytosis will typically give access to CNS delivery of small molecules but also nucleic acids or proteins via systemic and non-invasive administration [28]. Also, there is ongoing research to modulate nerve electrical activity or stimulate neural growth using gold nanoparticles combined with laser activation [29]. Such approaches open opportunities for the treatment of neurodegenerative diseases such as Parkinson's or Alzheimer's disease.

Furthermore, nanomedicine can become a key player in cross-sectoral and cross-technological solutions for healthcare. The unique properties of nanoparticles (electrical, mechanical, acoustic, optical) open new opportunities when combined with other technologies in health. Some examples of cross-technological solutions have been cited above. Furthermore, sensors should also be mentioned since their sensitivity, speed and miniaturization may be improved by nanomedicine. Such nanosensors will be suitable for more sensitive biomarker detection in a large panel of diseases (e. g. cancer, CNS and infectious diseases). A review of Munawar et al. gives a good overview of the potential of nanoparticles for nanosensors [30]. Typical applications of nanosensors are found in the monitoring and control of pandemics and plagues. There are now diagnostic tools that have been approved for diseases such as Ebola and the Zika virus, which had the potential to develop into global pandemics without nanotechnology-based products.

One major advantage of nanomedicines as designed objects over other medicinal products is their high level of uncoupling between their functional requirements (therapeutic effect & targeted delivery for instance) and their design parameters (nanoparticle & drug for instance), as could be described by the general theory of axiomatic design by Nam P. Suh in the 1990's [31]. In other terms, a very interesting feature of nanomedicines is to offer the characteristics of a generic platform in which modules can be replaced, improved or re-designed without the need to re-design the whole product from the beginning every time its function needs to evolve. For instance, by keeping the same nanoparticle structure, but only changing the drug it carries, any other therapeutic agents inside the particle or through fine tuning of the coating of the particle, one can adapt the product to new applications or subtypes of patients with the same disease, with better efficiency, and while keeping some advantages inherent with the core particle itself. Re-design of the whole product could also be done by functions uncoupling in two distinct nanoparticles. Decreasing the notion of compromise between the required physico-chemical properties allows a more efficient delivery of these functions improving the treatment benefit / risk ratio [32]. This is indeed not the case for small organic molecules & biologicals that need to go through a high number of constraints for each new application. Answering these new constraints require modifications in the drug design to optimize a specific function but such modifications may also lead to degradation of other functions in the same time. Indeed, each new nanomedicine has to follow a full clinical development and no specific regulation at this stage is available for them. Still, despite nanomedicines are often regulated as drugs, they are different from classical drugs. As complex manufactured objects offering tunable functions that can interact at sub-cellular level, nanomedicines are platforms to design & deliver better medical solutions, with personalized treatment capacities.

We have described in the last paragraphs examples of concrete outcomes of the nanomedicine field and new exciting products to come. But what is the average approval rate of nanomedicines compared to classical drugs? Is there a difference in different fields, e.g. in oncology vs other clinical applications?

He et al. calculated the success rate of nanomedicine formulations in oncology for the different clinical phases [33]. They showed that the success rate of nano-enabled cancer drugs in phase 1 is 94%, and this is attributed to their good safety profile often couple to the improved pharmacokinetic for the drug. Phase 2 and 3 success rates are respectively of 48 and 14%. With an estimated total success rate from phase 1 to approval of 6%; thus, nanomedicines perform better than conventional drugs in oncology, which have a success rate of 3.4 [34]. However, Prof. Park is right in saying that nanomedicine has been mainly focused on cancer, and that the clinical outcome for other clinical applications has been poor. Why is it that, outside of oncology, only a few nanomedicines reach clinical trials and market approval? We need to enable and support clinical development of new promising formulations for diseases that is not related to oncology [35]. But what should we do to support the entry of new promising formulations of nanomedicines into clinical trials?

The difficulties in clinical translation of nanomedicine are multiple and complex. Among them are: (i) lack of education in business management, especially at the academic level, (ii) difficulties in performing the pre-clinical characterization and safety assessment from early stages, due to lack of protocols and lack of access to characterization facilities, (iii) difficulties in scale-up and GMP manufacturing and (iv) uncertainty and fragmentation in the regulatory framework, especially for the most complex borderline products that combining multiple technologies [4,36].

The European Technology Platform on nanomedicine (ETPN) [2] is a think tank created in 2005 and set up together with the European Commission (E.C.) to address the application of nanotechnology in healthcare. The ETPN believes that involving industry will accelerate the development of promising ideas and provide the effective and safe healthcare products that patients need. Today, it gathers more than 130 member institutions from 27 different countries, representing the whole value chain of healthcare from academia, SMEs, industry, healthcare providers to national associations, scientific societies and policy makers. The ETPN has supported strong and smart public funding of the most promising R&D topics where Nanomedicine can bring something more through strategic inputs coming for all stakeholders, towards the E.C. for the last fifteen years. Complementarily, the ETPN acts also as a driving for force for industrialization of nanomedicine in Europe since 2014, detecting the best innovations of the field and facilitating their transfer from innovative design to clinical development through the nanomedicine Translation HUB, a global set of premium services, free-of-charge for the beneficiaries. This Hub is composed of three main pillars, custom mentoring, product characterization and GMP manufacturing, as represented in .

The Nanomedicine Translation Hub: Developed infrastructure to accelerate the development of the best nanomedicine projects from innovative design to clinical development. Translation HUB is not a linear process and innovative projects can benefit of each pillar independently.

First, the HealthTech TAB (Translation Advisory Board) [37] is a unique mentoring service in Europe, boosting selected HealthTech inventions to transform them into successful businesses. It is funded and managed by the NOBEL Project which is funded by the European Commission under the Horizon 2020 research and innovation program. The HealthTech TAB gives access to world-class expertise from former managers from Pharma and Medtech industry, successful entrepreneurs, heads of innovation agencies, etc. Together, they offer custom support to innovative project holders on specific issues for which they usually lack skills: IP management, regulatory aspects, business development, market access, scale-up, team building, fund raising, etc. Application for the TAB is open to all: start-up, SMEs, academics, individual entrepreneurs, industry, etc. This service is free-of-charge for its beneficiaries, as a service funded by the E.C. through the NOBEL Project. The HealthTech TAB has already supported +110 projects and helped its beneficiaries to raise +15M in fundraising.

Another pillar of the Translation HUB is the European Nanomedicine Characterization Laboratory (EUNCL) [38], a trans-European, transdisciplinary characterization infrastructure founded in 2015, providing a comprehensive and integrated set of preclinical characterization assays for the nanomedicine formulations, including physical, chemical, in vitro and in vivo biological testing. EUNCL supports European stakeholders to advance the translation of their products into the clinic, e.g. advancing from TRL 3 to TRL4 or higher. Since 2015 EUNCL has operated thanks to E.C. H2020 funding and has supported more than 30 nanomedicine developers, including SMEs, big pharma and universities, in the safety and quality assessment of their formulation. More than 30 Standard Operating Procedures (SOP) have been validated and shared with the community (http://www.euncl.eu/about-us/assay-cascade/).

Finally, the Nanomedicine formulation could also benefit of one of the three medium scale product lines regrouped in the third pillar funded by Europe: Nanofacturing, Nanopilot and Maciviva. These have been established for scaling up existing good manufacturing practice (GMP) pilot lines to a medium-scale sustainable manufacturing process for solid core nanopharmaceuticals and other medical nanobiomaterials were funded. Interestingly, as a logical continuation of these first publicly funded efforts to ensure easier scale-up of manufacturing for nanomedicines in GMP conditions, a new industry offer provided by contract development and manufacturing organizations has recently appeared in Europe, proving both the high relevance and clear need of this approach for technology providers in nanomedicine.

Nanomedicines are not officially regulated differently from small traditional drugs. To be successfully translated into the market FDA and EMA both require that nanomedicines meet the same safety, efficacy and pharmaceutical quality criteria applied to all drug products [39]. However, due to their unique and hybrid nature, the quality assessment of nanomedicine formulations pose substantial analytical challenges when compared to small molecular or biological drugs (e.g. antibodies). In fact, in addition to the measurement of identity, strength, potency, stability and impurities, bacterial endotoxins and bioburden of the different chemical ingredients, additional physico-chemical properties must be assessed for the final drug product (the final nanomedicine formulation). These assessed properties include particle size, size distribution and polydispersity, surface charge, drug loading and drug release profile, complex core-shell chemical and physical structure, chemical and size stability during storage and when in contact with biological media [40]. To add a layer of complexity, classical characterization methods are often not applicable to nanomaterials. Furthermore, more complex methodological approaches are needed in order to understand how nanomedicine properties could impact their safety and efficacy profiles (e.g. determined by their immunological effects, biodistribution, pharmacokinetics, metabolism, and degradation profile) in order to determine the specific critical quality attributes (CQAs) of each system.

The US National Cancer Institute Nanotechnology Characterization Laboratory (NCI-NCL, ncl.cancer.gov/about-ncl) and the European Nanomedicine Characterization Laboratory (EUNCL, euncl.eu) have unbiasedly supported nanomedicine developers, by providing access to their multidisciplinary characterization facilities, and also by promoting knowledge and educational exchange within the community. The two laboratories have jointly worked with other H2020 consortia (e.g. REFINE and SAFE-N-MEDTECH), regulatory bodies (EMA and FDA), metrology institutes and standard authorities (ASTM E56) in order to develop new standards and to promote a harmonized approach between Europe and the US. Unfortunately, despite their efforts, due to the complexity to standardize characterization approaches on various very specific nanomaterials, currently only a few standard methods for nanomedicine characterization exist. Major gaps have been identified in the lack of standardized methods to measure: (i) drug loading (free vs. encapsulated drug), (ii) particle stability in plasma, including drug release kinetics, (iii) surface properties and surface interactions with the biological environment and (iv) particle interactions with the immune system [[41], [42], [43]].

In this context EMA has recently published a Regulatory Science Strategic Reflection to 2025. One of five strategic goals and core recommendations proposed is Enabling and leveraging research and innovation in regulatory science, which includes to Identify and access the best expertise across Europe and internationally and Disseminate and exchange knowledge, expertise and innovation across the network and to its stakeholders. ETPN is aware of the clear need to support the EMA strategic aims to guarantee access to the best expertise across Europe including infrastructure such as the EUNCL and novel initiatives such as the Open Innovation Test Bed for nano-pharmaceuticals production to support the development of a harmonized regulatory framework for nanomedicine and borderline products combining different technologies in one cross-technological solution. In this context, ETPN will support the continuation of the activities of the European Nanomedicine Characterization Laboratory (EUNCL) as part of the ETPN Translational Hub by reaching out for opportunities to pursue continuous public funding which is needed to support developers to bring their products to the market. Moreover, ETPN will support international initiatives aiming to reduce the current fragmentation of the standardization and the regulatory body landscape, e.g. by leading the emerging EU-US Community of Research (CoR) in Nanomedicine, with an international collaborative group called EU-US Collaboratory under its umbrella. This initiative includes academia, R&D, regulators, metrology and industrial experts, and has been created in order to address the lack of validated harmonized and standardized physical-chemical measurements of nanomedicines under the leadership of the National Institute of Standard and Technology (NIST) from the US side and the Joint Research Centre of the European Commission on the European side [44].

The ETPN has recently made efforts to strengthen the European ecosystem for smart health technologies within the NOBEL project. From precision engineering to smart connected HealthTech, and from academic research to the clinic, NOBEL is creating a European HealthTech ecosystem, for the convergence of nanomedicine with photonics, robotics, biomaterials, smart systems, digital health and textile. NOBEL has three main missions: (i) to build an ecosystem, as a unique meeting place for all stakeholders from academia to industry, SMEs, clinicians and policy makers; (ii) to shape a common vision for the future of HealthTech in Europe, the Continuum of Integrated Care, incorporating the separate roadmaps of individual technologies, and showing how concretely these medical technologies may improve the whole journey of patients, for a more, preventive, predictive, personalized and sustainable medicine; (iii) to accelerate the transfer to market of the most useful disruptive medical innovations, through the funding of the HealthTech TAB.

By coordinating the NOBEL project since 2017, the ETPN pursues its successful contribution to bring healthcare solutions faster to the market and foster the strategic cross-sectorial approach and intensifies crosstalk between different technology communities which is needed to synchronize cross-technology innovation and developments necessary to advance, e.g. functionalized surfaces for regenerative medicine approaches or smart biosensors to ensure distant monitoring of patients and attenuate the acute phase of a disease. Nanomedicine as a horizontal and essential complementary technology with broad applications in many medical fields of the Continuum of Integrated Care will continue to be at the front of innovation in healthcare and the ETPN will support and foster nanomedicine in this new vision. The ETPN is strongly willing to keep on playing a key role in shaping the future of health technologies in Europe, encouraging their synergy in a medical problem solving approach rather than a techno-push approach, for more preventive, patient-centered and sustainable health care. Indeed, patients, and citizens in general, do not care about technology for the sake of it. They care about quality of life.

From an ETPN perspective, nanomedicine unquestionably makes a difference for patients. Even if we agree with Prof. Park that nanomedicine was overpromoted a few years ago as an immediate revolution and several promises of nanomedicine are still not achieved, we are entering a new period turning from academic development to proven clinical value. We need to be constructive in our approach and focus on the gaps to fill to accelerate nanomedicine translation into a more mature phase. The ETPN will continue to support nanomedicine development using its different platforms towards the integration of knowledge, communication, and cooperation between different stakeholders (including academia, industry, clinics, training patients/people and related associations), providing instruments to support clinical translation of new products and contributing to shape the nanomedicine and smart health technologies landscape in Europe and in the coming European research funding program Horizon Europe. ETPN is also actively supporting formation of open-minded young researchers in the field, which will be the future protagonists of ideas and innovations for the sustainable development of nanomedicine. European support to nanomedicine needs to remain a priority in the next Horizon Europe program, so this technology can continue to contribute with cutting-edge science and innovation as a provider of new solutions to tackle complex medical challenges. The ETPN is therefore actively contributing and will reinforce its participation in to future European initiatives, including Europe's Beating Cancer plan, the Mission Cancer, the Cluster Health, and the innovative European Partnership for Innovative Health (Public Private Partnership) which is a new and unique occasion to finally see the medtech, pharma and biotech industries work together in Europe. Nanomedicine will open new possibilities to support the development of early diagnostic tools and better treatments, in a new, more patient centered, era. But, nanomedicine should not act as isolated technology and the ETPN will continue to be a driving force in shaping a cross-technology environment, where nanomedicine interacts with other technologies to design cross-technological, multidisciplinary medical solutions for the benefit of the patients.

Matthieu GERMAIN and Agnes POTTIER are co-inventors of patent applications related to Hensify product (Nanobiotix) described in this article. Alexandre CECCALDI is employee of ETPN. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.

Credit authors statement

Matthieu GERMAIN: Writing - Original Draft. Review & Editing

Fanny CAPUTO: Writing - Original Draft. Review & Editing

Su METCALFE: Writing - Original Draft. Review & Editing

Giovanni TOSI: Writing - Original Draft. Review & Editing

Kathleen SPRING: Writing - Original Draft. Review & Editing

Andreas K. O. SLUND: Writing - Original Draft. Review & Editing

Agnes POTTIER: Review & Editing

Raymond SCHIFFELERS: Review & Editing

Alexandre CECCALDI: Review & Editing

Ruth SCHMID: Review & Editing

More here:
Delivering the power of nanomedicine to patients today

Abstract

Knowing the beneficial aspects of nanomedicine, scientists are trying to harness the applications of nanotechnology in diagnosis, treatment, and prevention of diseases. There are also potential uses in designing medical tools and processes for the new generation of medical scientists. The main objective for conducting this research review is to gather the widespread aspects of nanomedicine under one heading and to highlight standard research practices in the medical field. Comprehensive research has been conducted to incorporate the latest data related to nanotechnology in medicine and therapeutics derived from acknowledged scientific platforms. Nanotechnology is used to conduct sensitive medical procedures. Nanotechnology is showing successful and beneficial uses in the fields of diagnostics, disease treatment, regenerative medicine, gene therapy, dentistry, oncology, aesthetics industry, drug delivery, and therapeutics. A thorough association of and cooperation between physicians, clinicians, researchers, and technologies will bring forward a future where there is a more calculated, outlined, and technically programed field of nanomedicine. Advances are being made to overcome challenges associated with the application of nanotechnology in the medical field due to the pathophysiological basis of diseases. This review highlights the multipronged aspects of nanomedicine and how nanotechnology is proving beneficial for the health industry. There is a need to minimize the health, environmental, and ethical concerns linked to nanotechnology.

Keywords: nanotechnology, nanobiotechnology, nanomedicine, medical applications, diagnosis, disease treatment, drug-delivery, healthcare

The world is theorized to have accidentally formed via the Big Bang that occurred from an unstable microscopic-sized energized particle (atom). A single bit created an entire universe, and now scientists are working again on similar small particles to create marvels of science. From here, the world of nanoscience has arrived and taken a firm place in every aspect of science and technology [1]. The vision for nanotechnology was presented by Nobel Prize-winning physicist Richard P. Feynman, who proposed the application of more significant objects and mechanistic tools at a smaller tool and particle scale, as he believed that there is plenty of room at the bottom [1,2]. Nowadays, apart from physicists, scientists from multiple fields believe that in the future, nanoscale manufacturing technologies and instrumentation such as nanomachines, robotics, nanomedicine, and diagnostic devices, among many others, will bring grand biomedical miracles to the world of medicine and other industries [3,4,5,6,7].

Nanoscale pertains to the size of one-billionth or 109 m of a material. A new scientific field of science in the form of nanotechnology was created because it was observed that materials, products, and devices developed from nanoscale particles almost always exhibit properties different from those of large-scale bulk materials. This follows the basic principles of physics and chemistry that as the state of matter is composed of atoms, any changes in atomic size, shape, and arrangement directly affect the materials properties [7,8]. Scientists think that nanotechnology is the future of science and thus they are looking forward to benefitting from the application of nanotechnology in almost every possible way. The unique properties and behavioral features of nanoscale products have also drawn the attention of clinicians, physicians, and biological researchers [9,10]. The effort is on its way to applying unique quantum phenomena at the nanoscale to the fields of medicine, biomedical sciences, bioengineering, food technology, biochemistry, biophysics, and other disciplines of biology and medicine [10,11,12,13].

Forty years of revolutionary interaction among biology, medicine, and nanotechnology have led to present-day nano-biotechnology, which is now showing progressive application in multiple aspects of the medical field [14]. From disease detection to treatment, many medical issues such as disease diagnosis, drug discovery, personalized medical procedures, cancer treatment, pharmaceutical discoveries, as well as the latest medical tools and procedures, are now improving on the uses of nano-biotechnology [15]. Similar to regular vaccination approval, nano-based medicine and nanovaccines are also obtaining regular medical approval with the passage of time. Various nanotechnology-based diagnostic kits such as nanosensors, nanoparticle-based imaging agents, nanoparticle-based PCR Assays, Lab-on-a-Chip devices, along with modern drugs and medicines such as nanoparticle-based drug delivery vehicles, liposomal formulations and polymeric nanoparticles, Nanomedicines (such as Abraxane (nanoparticle albumin-bound paclitaxel) and Doxil (pegylated liposomal doxorubicin)), nanotechnology in gene therapy, nanoparticle-based vaccines, and antimicrobial agents, etc. are being commercialized for research and clinical usage [16].

Nanomedicine is a broad-spectrum field of science and technology that unites multiple streams of medical applications such as disease treatment and diagnosis, disease prevention, pain relieving technologies, human health improvement medicine, nanoscale technology against traumatic injury, and treatment options for diseases [12,15]. Thus, an interdisciplinary approach is being adopted to apply the outcomes of biotechnology, nanomaterials, biomedical robotics, and genetic engineering combined under the broad category of nanomedicine [17]. On a broader level, nanoscaling of medical technologies provides efficiency, a rapid response rate, and functional effectiveness in most biological and chemical processes used to manufacture medical materials. Thus, research provides constant hope for the upcoming new applications of nanomedicine [12,18].

In this review article, comprehensive analyses have been carried out to examine the application of nanotechnology specifically in the field of medicine. The most advanced form of nanotechnological applications have been highlighted with a slight emphasis on the previous uses of nanotechnology in the past few years of the 21st-century. Some modern medical applications, such as diagnostics, nanomedicine, regenerative medicine, and personalized targeted therapies, have also been included to bring into account the latest nanomedical applications.

Diagnostic sciences are now using nanodevices for early and rapid disease identification for further medical procedural recommendations. It also utilizes nanotechnology for the predisposition of disease at the cellular and molecular level to develop insights into treatment options [16]. Nanotechnology has the potential to revolutionize the field of healthcare diagnostics by improving the accuracy, sensitivity, and speed of medical tests [18]. One of the profound applications includes nanoparticle-based diagnostic imaging, in which nanoparticles can be attached to specific biomarkers to enhance imaging modalities such as magnetic resonance imaging (MRI), computerized tomography (CT) scans, and positron emission tomography (PET) scans, making them more sensitive, accurate, and specific [19]. Similarly, nanotechnology-enabled point-of-care diagnostic tests can quickly and accurately detect infectious diseases, cancers, and other illnesses, enabling timely treatment and prevention [9,19].

Biosensors are yet another dimension of application in which nanotechnology has enabled the development of highly sensitive biosensors that can detect even low levels of biomolecules in bodily fluids such as blood and urine, facilitating early detection and disease management [20,21]. Similar applications come in the form of microfluidic devices that incorporate nanomaterials and can be used to isolate and analyze specific cells, proteins, and genetic material, providing rapid and accurate diagnosis of diseases [19,22]. Another use may involve nanopore sequencing, which is a novel technology that uses nanopores to detect the sequence of DNA or RNA molecules, allowing for rapid and accurate diagnosis of genetic disorders such as cancer and genetic diseases [23].

Recent advances show that nanomedicine can be used in in vitro diagnostics sciences to increase the efficiency and reliability of disease apprehension [24]. This is achieved via nanodevices at the subcellular level, with samples prepared from human tissue, cell culture, body fluids, etc. [19,25,26]. In in vivo diagnostics, the nanomedicine approach is being used to develop devices capable of working, responding, and modifying within the human body with the sole purpose of early diagnosis of any irregularities in the human body that could lead to toxicity or tumor development events [22,27]. A few types of nanoparticles that are currently in use for diagnostic purposes include paramagnetic nanoparticles, nanocrystals, quantum dots, nanoshells, and nanosomes [28,29]. Overall, nanotechnology has enormous potential in healthcare diagnostics and is expected to play a significant role in the development of personalized medicine.

Nanotechnology and Lab-on-Chip Technology have revolutionized the field of healthcare by offering innovative solutions for disease diagnosis, personalized treatment, and drug delivery [15]. The combination of these two technologies has led to the development of advanced diagnostic tools that are faster, more accurate, and more cost-effective than traditional diagnostic methods [30]. Lab-on-Chip technology is making progress in different fields of science; for example, it is being considered for use against viral and cancerous diseases [15,24]. The whole process revolves around analyzing genetic information at the cellular level [30]. Advanced procedures of gene sequencing and body fluid sampling have further assisted in revolutionizing nanotechnology in service of cures for diseases that were previously unimaginable [31,32].

Together, these two technologies have led to the development of Lab-on-Nanoparticles, which are small devices that can perform multiple functions, including diagnostics, drug delivery, and monitoring of various health conditions [31,32]. These devices are made up of nanoscale materials that can detect and respond to changes in the body, allowing for real-time monitoring and personalized treatment [26]. One of the significant applications of nanotechnology and Lab-on-Chip Technology in healthcare is cancer diagnosis [20,21]. Nanoparticles can be designed to target cancer cells, allowing for early detection and treatment [33]. Lab-on-Chip devices can also be used to diagnose various health conditions, including infectious diseases, genetic disorders, and metabolic disorders [32,34].

The use of nanotechnology and Lab-on-Chip Technology in healthcare has also led to the development of advanced drug delivery systems [31]. Nanotech systems such as nano-Liposomes can target specific cells or tissues in the body, enhancing drug efficacy and reducing side effects [28,35]. Moreover, viral detection is considered a feature that will be linked to future generations of nanoscale diagnostic devices. Such devices are expected to enable the detection of the release of medications in the organs of the body, which will help in the calculation of treatment efficiency and efficiency rates [36]. In simple terms, nanotechnology is trying to increase the pharmacokinetic and pharmacodynamic properties of drugs to stay longer inside the body, work faster and more efficiently, and at essential sites [37].

A brief overview of nanotechnological applications in pharmaceutical sciences has been covered in the following section with a diagrammatic representation in .

Applications of nanotechnology in pharmaceutical sciences.

Nanoscience has revolutionized the pharmaceutical industry by enabling the production of improved therapeutic drugs with enhanced efficacy and lower toxicity. Nanoparticles can improve the pharmacokinetics of drugs by increasing their solubility, stability, and bioavailability [38]. They can also target specific tissues and cells, reducing side effects and enhancing their efficacy [25]. The nanoscale size and unique physicochemical properties of nanoparticles demand precise specifications in terms of drug dose and administration [39,40]. The dose of nanoparticles depends on various factors such as their size, shape, surface properties, and the method of administration [40]. For instance, oral administration may require a higher dose to achieve the same effect as intravenous administration due to the differences in absorption and biodistribution [40,41].

Furthermore, nanoparticles have complex pharmacokinetics and dynamic behavior in vivo, requiring a careful consideration of their dose regimen [40]. Researchers need to determine the optimal dose range, frequency, and duration of nanoparticles to achieve their therapeutic goals while minimizing adverse effects [41,42]. In the past, medical studies have resulted in very advanced treatment options; however, there is still a gap in effectively neutralizing drug overdoses. The use of nanoparticles as absorbents of toxic drugs is a feature being taken into account to create a rich method of drug absorption in the medical sciences [40,41,42]. The design of nanosponge-type substances is on the way to absorb unnecessary toxic dosages of drugs in blood to reduce the side effects of drug overdoses and treat ailments from body fluids [43]. Such antiviral drug absorbents have been introduced by researchers that work as nanoscale molecules to render anticancer and antiviral nucleoside analogs by linkage with squalene [44]. These nano-assemblies work as superior anti-cancerous molecules to treat human cancer cells that have yet to be developed beyond in vitro studies [45]. In summary, the development of nanomedical products requires careful consideration of the dose and administration of nanoparticles to ensure their efficacy and safety. The nanoscience community must collaborate with regulatory agencies to develop guidelines for nanomedicine testing to ensure their safety and efficacy.

Nanotechnology has revolutionized the field of drug delivery by providing an effective and targeted delivery of drugs, minimizing side effects, and increasing the therapeutic efficacy of drugs. The application of nanotechnology in drug delivery involves the use of nanoparticles that are designed to carry drugs and deliver them to the desired site of action [46]. The use of nanotechnology in drug delivery has several advantages. First, it allows for targeted and controlled delivery of drugs to specific sites in the body, such as tumors, inflamed tissue, and infected areas [46]. This reduces the amount of drugs required and minimizes side effects. Secondly, nanoparticles can improve the solubility and stability of drugs, making them more effective in treating diseases [47]. Thirdly, nanotechnology can increase the bioavailability of drugs by enhancing their absorption and distribution in the body. This allows for lower doses of drugs to be used, resulting in reduced toxicity [48,49].

Drug delivery technologies are also being given full consideration to be modified as per the new rules of nanoscaling. Some kinds of medical nanorobots are in line to be used for medicine delivery [32]. These materials swim across veins and carry drugs to specific sites. These aspects are being used for antitumoral responses of drugs [48]. Scientists are even working on performing wireless intracellular and intranuclear nanoscale surgeries against multiple malignancies and diseases [46,48]. Marvelous scientific arrangements are being carried out in the form of manufacturing and testing mechanical red blood cell technologies called respirocytes. Nanorobotics share the potential to deliver 200+ times more oxygen to body tissues as compared to natural red blood cells [49,50]. This could make one think about the potential of nanotechnology to be utilized for the diagnosis and treatment of various blood-linked disorders and their cure in the future [50]. In conclusion, the application of nanotechnology in drug delivery has revolutionized the field of medicine. It has provided an effective and targeted delivery of drugs, minimized side effects, and increased the therapeutic efficacy of drugs. The future of drug delivery lies in the continued development of nanotechnology-based drug delivery systems.

DNA-based drug delivery devices have been introduced in the past few years, such as DNA guns and DNA vaccines. Based on similar principles, an emerging field of DNA nanotechnology is being introduced in the nanomedicine industry [51]. These medical tools allow for the self-assembly of nanostructures and molecules that ultimately enhance drug targeting and reduce the toxicity associated with these drugs. With such technology, toxicity measures can be easily dealt with in diseases such as cancer, where the major issue is the drug toxicity associated with chemotherapeutic drugs [24,51].

The latest advances in research indicate that modern programing optimization and in silico approaches are being adopted to design DNA nanostructures with precise size, structure, surface chemistry, and functioning properties against specific diseases [22,52]. The effort is also to create personalized targeted drug therapies using nanotechnology-based DNA medicine [51]. Efficient drug biomolecules, such as doxorubicin and CpG oligonucleotides, have been successfully amalgamated with DNA-based nanostructures to increase cellular intake efficiency [53]. The future holds the potential to create RNA-based medication using principles similar to those employed in DNA-based medication [54].

Nanobiotechnology and gene therapy are two fields that often intersect in the development of innovative therapeutic approaches for the treatment of various diseases. In gene therapy, DNA molecules are introduced into the patients cells to replace defective or missing genes, with the aim of treating genetic disorders and other diseases [55]. One application of nanobiotechnology in gene therapy is the use of nanoparticle-based delivery systems to transport therapeutic genes to target cells [41,56]. These nanocarriers protect the DNA molecules from degradation and enhance their ability to penetrate the cell membrane, increasing the efficacy and safety of gene therapy [53,56].

Other nanobiotechnology approaches that support gene therapy include the development of gene editing technologies that use nanoscale tools to precisely modify DNA sequences and correct genetic mutations [57]. Additionally, nanoparticle-based sensors can be used to monitor gene expression and other molecular events in real-time, providing valuable information for personalized medicine [32]. Modern therapeutic concepts including gene therapy and molecular DNA-based therapies are already being practiced in healthcare and the arrival of nanotechnology has forwarded further advances in it [58]. Since the very basis of working gene therapy is at the molecular level of disease prevention and genetic adjustments, nanoscale technology plays a vital role in gene therapy [58].

Gene therapy processes are being modified to attach different kinds of biodegradable and non-biodegradable organic and inorganic particles fabricated with nano-assemblies. These structural combinations help bind DNA and access it across cellular surfaces [59]. Moreover, polymer-based nanoparticle mixtures are also prepared for intravenous drug injections. These modified technologies are a gateway to further advances in nanogenetic therapies [60]. Overall, the integration of nanobiotechnology and gene therapy is expected to lead to advanced treatments for a wide range of diseases, including cancer, genetic disorders, and infectious diseases.

Polyplex micelles are a type of nano-sized structure that are formed by the self-assembly of cationic polymers with nucleic acids, such as small interfering RNA (siRNA) or plasmid DNA (pDNA) [61]. These polyplex micelles have attracted significant attention for their potential in gene therapy and as drug delivery systems. In the context of tumor treatment, various polyplex micelle-based strategies using siRNA and pDNA have been studied. siRNA is an RNA molecule that is used to specifically target and knock down the expression of disease-related genes [62,63]. Plasmid DNA (pDNA) is a circular DNA molecule that can carry therapeutic genes to the target site. Polyplex micelles can encapsulate siRNA or pDNA within their core, protecting them from degradation and facilitating their delivery to tumor cells [63,64]. Additionally, the cationic nature of the polyplex micelles allows for electrostatic interactions with the negatively charged cell membrane, promoting their uptake by tumor cells [64].

These polyplex micelle-based strategies have been investigated for the treatment of various tumors, including pancreatic adenocarcinoma [63]. Pancreatic adenocarcinoma is a particularly challenging type of solid tumor resistant to many conventional treatment options. By using polyplex micelles, siRNA or pDNA can be delivered specifically to the tumor cells, enabling targeted gene therapy or enhancing the efficacy of chemotherapeutic drugs [64]. Thus, nanotechnology, specifically polyplex micelles, offers a promising approach for delivery of siRNA or pDNA to tumors such as pancreatic adenocarcinoma. These micelles can protect genetic material, promote cellular uptake, and potentially enhance the effectiveness of treatments for intractable solid tumors [65].

Nanomedicines are largely produced through chemical and physical methods of downgrading particles up to micro- and nanoscales. However, with the concerns of environmental and toxic health impacts, nanomedicine is now employing the concept of green chemistry and green engineering into the manufacturing of nanobiomedicine [66]. The purpose of this green technology is to create eco-friendly nanoassemblies with less environmental and health-related negative impacts [66]. Subsequently, the combination of green nanoassemblies with drugs, vaccines, or diagnostic markers will be the next step to propel the field of green nanomedicine. Many inorganic nanoassemblies have been introduced to the market and manufactured on the principles of green engineering and nanotechnology [67]. Some examples may include gold and silver nanoparticles, quantum dots, organic polymeric nanoparticles, mesoporous silica nanoparticles, dendrimers, nanostructured lipid carriers, solid lipid nanoparticles, etc. [66,67,68].

These nanoassemblies are attached with drugs, DNA molecules, or specific enzymes, proteins or peptides for further handling in nanomedicine purposes [66]. However, the need is to establish research studies that demonstrate the difference and effectiveness level of nanomedicine produced using normal bioengineering against that of manufacturing of nanomedicines through the elaborative principles of green bioengineering [66,67,68]. This will allow scientists to opt for the best manufacturing conditions for nanoassemblies in the future.

The causative agents of viral, bacterial, and other microscopic diseases work at the microscopic level; therefore, the best way to fight against them is at the nanoscale. Nanotechnology is thus the gateway to the cure and diagnosis of a wide range of viral, bacterial, and fungal diseases [69]. Although traditional Greek medicinal practices have been using metals such as silver to cure diseases for a long time, an updated version of nanoscale-based material conversion has been shown to improve the efficiency of such traditional and modern medication options [70]. One such study carried out by Nycryst Pharmaceuticals (Canada) showed that nanosized silver particles are more reactive to cure burn or wound as they easily penetrate the skin at some small scale [71].

The genomic and proteomic fields are already contributing much to the elucidation of molecular insights into disease, and with the assistance of nanotechnology, new opportunities are being put in the hands of researchers to create powerful diagnostics tools with the power of genetic elucidation of irregularities at the level of the gene [72]. Research indicates that soon, nanotechnology-based diagnostic and treatment options will be available for preventive and regenerative medicine with targeted and personalized therapy potential against pathogenic and pathophysiological diseases [70,71,72,73]. All these benefits are coupled with the cost-effective and time-saving aspect of this new technology.

There are several barriers or issues associated with nanoparticles in terms of delivery efficiency and clinical translation. The accumulation of nanocarriers in organs of the reticuloendothelial system, especially the liver, poses a significant challenge for clinical translation as it captures a majority of the injected dose, hindering the delivery of an adequate dose to the targeted disease site and potentially causing toxicity concerns [74]. Researchers have developed various approaches to address this issue, including preconditioning macrophages with chloroquine, saturating the reticuloendothelial system organs with drug-free nanocarriers, and transient stealth-coating scavenger cells to enhance the efficiency of drug-loaded nanoparticles reaching the diseased tissue [75,76,77]. Additionally, the incorporation of targeted cellular on the surface of nanocarriers such as those applying the do not eat us strategy, helps evade capture by the reticuloendothelial system, improving the accumulation of nanodrugs at the desired site [73,76].

On the other hand, surface shielding of nonionic hydrophilic polymers such as PEG on nanocarriers reduces cellular uptake and endosomal escape, resulting in poor delivery efficiency despite improving colloidal stability and stealth in a biological environment [77]. To overcome this stealth dilemma, targeting ligands are strategically placed at the distal end of the PEG segments to facilitate specific ligand receptor-mediated uptake [78]. Another strategy involves wrapping anionically charged polymers on positively charged mRNA-polyplexes to promote endosomal escape by converting them into positively charged polymers in response to the acidic pH of the endo/lysosomal compartments [79].

The use of messenger RNA (mRNA)-loaded lipid nanoparticles is limited by their hepatic protein expression, even when administered locally through intramuscular and intratumor injections [80]. Minimizing the off-target hepatic expression would be advantageous for protein replacement therapies and cancer immunotherapies. One approach involves incorporating microRNA target sites in therapeutic mRNAs to selectively prevent their expression in the liver [80]. Some other generalized barriers associated with nano-based drug delivery mechanisms are included in . It is important to note that although nanoparticles face these barriers and issues, significant advancements are being made in addressing them, bringing us closer to their successful clinical translation.

Barriers associated with nano-based drug delivery.

Nanotechnology is the science of creating and manipulating materials at the molecular and atomic levels. Bone regeneration technology creates new bone tissue, or helps existing bone tissue heal, with the use of materials that promote bone growth [81]. Nanotechnology is increasingly used in bone regeneration technology to create better, more precise and targeted materials for promoting bone growth [80]. For example, researchers are exploring the use of nanoparticles to deliver drugs or other molecules that promote bone growth directly to the areas that need them, improving the effectiveness of the treatment [80].

Nanoparticles can also be used to create scaffolds that mimic the structure of bone, which can help guide new bone growth and aid in bone regeneration. Additionally, advances in 3D printing technology that uses nanoscale materials can be used to create highly precise and customized implants for bone regeneration [81]. Bone weakening and dysfunction is a widespread problem and this has been marked by nanotechnologists as an issue of the utmost importance when linking nanotech to medicine. Some studies are being carried out regarding bone formation and structuring with the help of nanotechnology [80,81]. Scientists are trying to develop bone graft substitutes in the form of nanostructured materials with similar properties to be accepted by body and organ tissues. If these studies succeed, they will bring a new wave of regenerative technology to cure damaged bones and broken muscular fragments [82].

Principle investigation on biomineralization is being carried out to reduce the particle size of bone materials that could be coupled with its crystalline properties to be embedded into collagen fibers [80]. The purpose is to create a penetrating composition in damaged bone areas with specific mechanical properties to revolutionize the field of osteology and bone tissue engineering [80,81]. Similar studies are being carried out to make artificial joints, nanoscale collagen-mimicking coatings for knees and hips that act to stabilize the process of bone formation by osteoblasts [83,84]. Overall, the use of nanotechnology in bone regeneration technology holds great promise for improving the outcomes of bone repair and regeneration, including faster healing times, improved bone strength, and reduced complications.

Regenerative medicine is an interdisciplinary field of medical applications in which the benefits of cell therapy and tissue engineering methods are well fabricated to device mechanisms for the treatment, maintenance, improvement, and reparation of damaged and dead cells, tissues, and organs [73]. Previously, it was difficult to deal with the body at the cellular level but with the emergence of nanoscale technology, a huge opportunity has become available in the form of regenerative medicine to interact with cells and their components so that the linked cellular responses and extracellular material production can be controlled [80]. Tissue repair has been greatly upgraded with the powerful tissue regeneration abilities of nanoassemblies. These technologies are being directed for cellular adhesion, migration, differentiation, and other mechanical aspects that initiate tissue regeneration [85].

Exploration in the field of nanomedicine is going on to manufacture nanoscale materials, such as gold and silver nanoparticles, dendrimers, nanorods, carbon buckyballs, nanoshells, nanocubes, and many other forms of nanoparticles [73,79]. Each is specific to its linked properties, which can be directly utilized in targeted tissues and organs. Multiple research groups are working worldwide to explore the diagnostic, therapeutic, anti-viral, antifungal, and most importantly anticancerous properties of these nano-agents [70,72,86]. Progress shows that soon, a world of nanotechnology will bring a revolution to the treatment options for incurable diseases such as cancers, for which early diagnosis through nanotechnology is already on board and has been successfully explored [73,86].

A brief overview of nanotechnological applications in surgery is covered in the following section with a diagrammatic representation in .

Applications of nanotechnology in surgery.

Surgical nanorobotics involves the development and use of tiny robots or nanorobots that can perform surgical procedures with high precision and efficiency [87]. These nanorobots can be guided to specific locations within the body using advanced imaging techniques, and they can then perform tasks such as delivering drugs, removing tumors, or repairing damaged tissues. Nano-bioelectric medicine, on the other hand, involves using electrical signals to stimulate the bodys healing processes [88,89]. This emerging field focuses on the use of nanoscale technologies to access and control the electrical activity of cells and tissues in order to treat a wide range of medical conditions, including chronic pain, wound healing, and heart disease [90]. Both surgical nanorobotics and nanobioelectric medicine have the potential to revolutionize the field of medicine and improve patient outcomes. However, there is still much research needed to fully explore the potential of these technologies and ensure their safety and efficacy [88].

Programming, engineering, and biological fields are working inter-connectively to develop a surgical nanorobot that works through the vascular system. These small-scale devices are manufactured with the multipurpose function of searching diagnostics and treatments against lesions and pathogens [87,88]. These robots work at a minute scale that can be used to cut even a single dendrite and neuron at the cellular surgery level without causing harm to other neurons bound in a complex network. These experiments have been confirmed in animal models where a nanoscissor action has been governed by these nanorobotics [91]. The results have pushed scientists to perform further experiments before optimizing surgical conditions on diseased patients. A new wave of bioelectric medicine is also in the market which adheres to biological components for more effective diagnostic and therapeutic therapies. This nanobioelectronic is being employed in cancerous diseases, cardiovascular disorders, and other malfunctions in the human body [92]. However, many improvements are needed to successfully apply this technology in a clinical setting for multipronged complex diseases.

Nanogenerators, as the name indicates, are a class of self-powered and implantable medical nanosensors. They work on the principle of conversion of mechanical energy from body movement into an electric spark [87]. As the body converts chemical energy from glucose, muscle converts this energy to mechanical energy and in turn these nanogenerators convert it into electric energy which can be used to charge and power implantable nanodevices that are aggressively being manufactured for medical purposes nowadays [88]. Implantable medical nanogenerators (IMNGs) are miniature devices that use mechanical energy from body movements to generate electrical energy [87]. They can be implanted inside the human body and used to power various medical devices, including pacemakers, neurostimulators, and drug delivery systems [93].

IMNGs are made up of thin layers of materials, such as piezoelectric materials, which convert mechanical energy into electrical energy. These materials generate electric charges when they experience mechanical stress, such as bending or pressure [87]. They can also be designed to harvest energy from other sources, such as temperature changes or fluids in the body [88]. IMNGs have several advantages over traditional batteries used to power implantable medical devices. They can eliminate the need for battery replacements, which can be invasive and costly. They can also improve device reliability as battery failures can cause serious medical problems [93]. Additionally, IMNGs are environmentally friendly since they do not require the disposal of toxic batteries [94].

Despite their potential benefits, there are still challenges to overcome in developing IMNGs. The devices must be durable enough to withstand the harsh conditions inside the body, including high temperatures and corrosion from body fluids [95]. They must also be small enough to be implanted inside the body without causing discomfort or obstruction [94,95]. Overall, IMNGs hold great promise for improving the safety, reliability, and convenience of implantable medical devices in the future. Therefore, researchers are continuously working toward their development to make them practical for human use.

Anesthesia induction is a critical step in dental surgeries and other sensitive medical procedures, such as brain surgeries. For such anesthesia induction procedures, researchers are working on nanorobotic suspension mixtures that make a colloidal suspension with millions of nanoscale active analgesic nanoparticles [96]. These nanoparticles work on patients gingival and other sensitive portions and penetrate deep up to the level of loose tissue. This passage of nanomaterials is conducted via the combinational principles of chemical and temperature gradients and positional navigation that are monitored and controlled by onsite nanocomputers [97]. This nanoscale anesthetic action helps to carry out the desired effect, attained quickly with an even distribution of anesthetic in the projected organ such as the dental surface. The sensitivity action can also be controlled for a particular tooth for which surgical action is required. After the completion of surgeries, nanorobots are controlled via nanocomputers to restore tooth sensitivity to normal [98].

Nanodentistry is a separate branch of nanomedicine that involves a broad range of applications of nanotechnology ranging from detection to diagnosis, to cure treatment options and prognostic details about tooth functions [99]. A wide spectrum of oral health-related issues can be dealt with using nanomaterials [100]. These nanomaterials derive their roots from tissue engineering and biotechnologically manufactured dental nanorobotics [100,101]. Some recent advances under oral nanotechnology may include treatment options such as anesthesia, dentition renaturalization, hypersensitivity cures, orthodontic realignment problems, and modernized enameling options for the maintenance of oral health [99,102].

The nanoscale technology used for such functions are named mechanical dentifrobots. They work to sensitize nerve impulse traffic at the core of the tooth in real-time calculation and hence could regulate the tooth tissue penetration and maintenance for normal functioning [103]. The functioning is coupled with programmed nanocomputers to execute actions from external stimuli via connection with the localized internal nerve stimuli. These mechanistic insights could help dental surgeons suggest a strategic treatment option that may be conducted directly via in vivo nanorobot action using acoustic signals, as elaborated earlier [100,101,102,103,104]. Some of the applications of nanotechnology in the field of dental science have been compiled at the end of this section in .

Major applications of nano-dentistry.

Scientists are further working to use nanotechnology for the creation of dental cures and treatment strategies. This may include the stimulation of the natural biomineralization process or the utilization of nanomaterials for artificial tooth development with sensitivity programed by nanorobotics [100,105]. They are trying to develop the hardest tissue enamel by using nanoscale manufacturing of nanorods derived from calcium hydroxyapatite crystals to help regulate the function of teeth. Additionally, reconstructive dental nanoparticles are utilized to offer patients a rapid and long-term cure against hypersensitivity [106].

Repositioning of the tooth is a matter of greater concern for patients as it sets the basis for further cure or disruption of dental health in case of maladjustment. Orthodontic nanorobots could be used in this case to manipulate tissues in such a way that a smooth painless straightening, rotation, and repositioning of the tooth could be attained [107]. Moreover, with time, customers are more interested in improving the aesthetic standing of their physical appearance, and so the concept of dental esthetics has emerged. In this regard, nanotechnology is considered to perform actions such as excavating dental amalgams or remanufacturing teeth alongside fillings, crowns, and other such modifications [107,108].

Much more effort is being put into securing dental durability and the appearance of teeth in normal dentistry practices. Nanotechnology provides a more secure and long-lasting solution in the form of nanostructured dental materials with carbon nanotubes that provide fracture-resistant properties [109]. Additionally, simpler dentifrobots are being incorporated into mouthwashes and toothpastes to replenish dental surfaces on a routine basis for cleaning and continuous calculus debridement [110]. These dentifrobots have the ability to highlight and destroy specific pathogenic bacteria from the mouth and retain the useful oral microflora in a healthy balance [111]. All these benefits delay the conventional causes and processes of dental decay with the remedial disappearance of oral diseases, especially in the early years [100,112].

In the world of medicine, complex and incurable diseases such as cancer are always given a special focus to find treatment and early diagnosis options for these modalities [113]. Nanotechnology is providing a good opportunity for researchers to develop such nano-agents, fluorescent materials, molecular diagnostics kits, and specific targeted drugs that may help to diagnose and cure disease in a better way in the future [114]. Scientists are trying various protocols to conjugate already available drugs with nanoparticles to enhance drug specificity and targeting in organs [113,114,115].

Nanomedicine acts as the carrier for hundreds of specific anticancerous molecules that could be projected at tumor sites. Moreover, the tumor imaging and immunotherapy approaches linked with nanomedicine must also be kept in mind when diving deep into nanomedicine and cancer links [34]. The effectiveness of nanomaterials in cancer therapies has pushed scientists to replace traditional cancer therapy approaches with targeted therapies that may be utilized alone or in conjugation with already available anti-cancerous drugs [16,34]. The focus is also being drawn toward lessening the impact of chemotherapeutic drugs by increasing their tumor-targeting efficiency and improving their pharmacokinetic and pharmacodynamic properties. Similarly, heat-induced ablation treatment against cancer cells alongside gene therapy protocols are also being coupled with nanorobotics [52].

Some other cancer treatment options, in the form of enhanced tissue imaging and tumor microenvironments, as well as adjustment by the release of nanoparticle-bounded drugs, are being practiced in the oncology field [59,116]. These nanomedicines hold the potential to overcome drug solubility, instability, and resistance issues. Various nanomedicines that act as anticancerous medicines are being researched, while some have been approved by the US Food and Drug Administration (FDA) and European Medicine Agency (EMA) [117]. These anticancerous drugs may utilize the Enhanced Permeation and Retention Effect (EPR effect) and/or active targeting of nano assemblies such as liposomes, albumin nanospheres, micelles, and gold nanoparticles [118]. Some of the applications of nanotechnology in the oncology field are discussed in the following section and a summary () is shown at the end of this section.

Applications of Nanotechnology in Oncology field.

Cancer diagnosis is the most observable problem in cancer patients. Cancer largely remains uncured due to late detection in the third or fourth stages. To fight this cause, nanotechnology is being employed to allow early detection of tumors in organs [16]. Nanotechnology provides a very sensitive and specific multiplexed measurement capacity to detect cancer biomarkers in extracellular settings and in vivo bioimaging techniques [19]. Nanotechnology has enormous potential in the field of cancer diagnosis. Nanoparticles are incredibly small and can penetrate cell walls and the bloodbrain barrier. This makes them ideal for delivering drugs and other therapeutic agents to cancer cells. They can also be used to detect cancer cells and identify the location and nature of the disease [119].

One of the most promising areas of nanotechnology in cancer diagnosis is the development of targeted nanoparticles. These are nanoparticles designed to adhere specifically to cancer cells, allowing them to be easily identified and targeted by doctors. This could result in more accurate early detection, better monitoring of cancer progression, and faster diagnosis [120]. Another promising application of nanotechnology in cancer diagnosis is in the development of biosensors. Biosensors are small devices that can detect specific biomarkers in a patients blood or other bodily fluids. These biomarkers can be indicative of cancer and could be used to detect cancer at an early stage [92,93].

In conclusion, nanotechnology has enormous potential in the field of cancer diagnosis. With targeted nanoparticles and biosensors, it could help in the development of a more accurate, non-invasive and effective way to diagnose cancer. However, the challenges pertaining to such diagnostic kits remain and the need is to overcome these challenges and update the nanotechnology-based diagnostic methods for cancer and other disease diagnostics and prognoses in the future [19,120].

Multifunctional theranostics therapy is an emerging field in cancer treatment that combines multiple modalities into a single treatment approach. This approach aims to both diagnose and treat cancer using nanomaterials. Nanomaterials, such as nanoparticles, are highly versatile due to their unique properties at the nanoscale [121]. They can be engineered to have various functionalities, such as imaging capabilities, drug delivery systems, and targeted therapy agents. By using these multifunctional nanomaterials, theranostics therapy can provide simultaneous cancer diagnosis and treatment [122]. In parallel, the term multimodal refers to the combination of multiple treatment modalities in a single therapy [123]. In the context of theranostics therapy, multimodal treatment can involve different approaches, such as chemotherapy, radiotherapy, and immunotherapy [124]. These modalities can be incorporated into nanomaterials used for therapy, allowing for targeted delivery and enhanced efficacy. The theranostic approach also enables real-time monitoring of treatment outcomes [124]. By incorporating imaging agents into nanomaterials, clinicians can track the distribution and effectiveness of the therapy. This information helps guide treatment decisions and allows for adjustments to optimize patient outcomes [123]. Thus, the combination of multifunctional and multimodal theranostics therapy using nanomaterials holds great promise in the fight against cancer. It offers the potential for personalized and targeted treatment, improved efficacy, and reduced side effects compared to traditional cancer therapies [121,125].

Targeted nano drug delivery technology for cancer therapy is a form of treatment that uses nano-sized particles to deliver drugs specifically to cancer cells in the body. These nanoparticles can be engineered to selectively bind to cancer cells, allowing the drugs to be delivered directly to the tumor site, while minimizing damage to healthy tissues [5]. The development of targeted nano drug delivery systems has several advantages in cancer therapy. Firstly, it can enhance the efficacy of the drugs by increasing their concentration at tumor sites. This is especially important for drugs with low solubility or high toxicity as it allows for higher doses to be delivered directly to the cancer cells [24]. Additionally, targeted nano drug delivery systems can help overcome some limitations of traditional chemotherapy, such as poor drug bioavailability or resistance. By encapsulating the drugs within nanoparticles, their stability and solubility can be improved, leading to better drug delivery and higher therapeutic effects [5,126].

There are various types of targeted nano drug delivery systems being explored, including liposomes, polymeric nanoparticles, dendrimers, and carbon nanotubes. These nanoparticles can be functionalized with ligands or antibodies that specifically bind to receptors or proteins overexpressed on the surface of cancer cells [127]. This targeting moiety allows for the selective binding and internalization of nanoparticles into cancer cells, enabling efficient drug delivery. Furthermore, targeted nano drug delivery systems can also be combined with imaging agents, enabling real-time monitoring of drug distribution, tumor targeting, and uptake [24,128]. This helps in tracking the therapeutic response and adjustment of treatment protocols as needed [128]. Overall, targeted nano drug delivery technology has the potential to revolutionize cancer therapy by improving the efficacy and safety of drugs, minimizing systemic side effects, and enabling personalized medicine approaches. However, further research and development is still needed to optimize these systems and ensure their clinical translation [128,129].

Nanotechnology and magnetic drug delivery technology are both innovative approaches in the field of medicine that improve drug delivery and enhance treatment effectiveness. Magnetic drug delivery technology utilizes the application of an external magnetic field to guide drug-loaded nanoparticles to a specific site within the body [130]. Magnetic nanoparticles can be functionalized with drugs and then injected into the bloodstream. By applying a magnetic field externally, the nanoparticles can be directed toward the desired location, such as a tumor [131]. This approach allows for more precise drug delivery, minimizing systemic exposure and reducing side effects [39]. Similarly, by engineering nanoparticles, researchers can create drug carriers with unique properties that are not in conventional drug delivery systems [130,131,132]. These nanoparticles can be functionalized and designed specifically to target diseased cells or tissues, improving drug concentration at the desired site and minimizing off-target effects [131].

Additionally, nanoparticles can protect the drug payload from degradation, resulting in improved stability and prolonged drug release. Thus, the combination of nanotechnology and magnetic drug delivery technology has shown promise in several areas of medicine [130]. For example, in cancer treatment, magnetic nanoparticles can be used to deliver chemotherapy drugs directly to tumors, increasing drug concentration at the tumor site and reducing toxicity in healthy tissues. This approach can enhance treatment efficacy while minimizing adverse effects [133]. Furthermore, magnetic drug delivery can also be utilized in targeted therapy for other diseases, such as neurological disorders. Nanoparticles loaded with neuroactive drugs can be guided to specific regions in the brain using externally applied magnetic fields, allowing for more targeted treatment and potential reduction in systemic side effects [133]. Thus, the integration of nanotechnology and magnetic drug delivery technology has the potential to revolutionize drug delivery by improving targeting, reducing side effects, and enhancing treatment outcomes. Ongoing research and development in this field hold great promise for the future of medicine.

As nanotechnology is making progress in the field of medicine and biological sciences, eyes are on the board as to how this technology will bring revolution to medical machinery [25]. It is predicted that soon, micro and nanoscale materials will be integrated with useful robotic characteristics that may include nanoscale manipulator arms, sorting rotors, reagent purification kits, and super diagnostic surfaces that will be modeled to respond to particular disease diagnostics and treatment. These nanomaterials and robotic connections are assumed to be controlled via nanocomputers [25,134].

Nanocomputers are expected to control, activate, deactivate, and deter the response rates of nanomechanical devices [134]. They will be programed to execute specified medical and dental operations with a connection to a wider network of interconnected nanocomputers, such as programmed nanomachines and robotics, which have the potential to allow physicians and clinicians to perform precise medical procedures at a subcellular level [135,136,137]. Furthermore, these robotic elements are expected to work in gerontological and pharmaceutical research phases, diagnostics, and dentistry [138].

In addition to the application of nanomedicine to humans, beneficial applications of nanomedicine are now being used on animals. Multiple variations of nanovaccines and nanoadjuvants have started their way into veterinary sciences [11,139]. The previously used animals therapeutic, diagnostic, treatment, and veterinary vaccinations along with disinfection, breeding, reproduction, and nutritional concerns are now being modernized using the concept of nanotechnology [139].

Nanotechnology has the potential to revolutionize the field of veterinary medicine, offering new diagnostic tools and treatment options for animals. In the area of diagnostics, nanotechnology can improve the accuracy and sensitivity of diagnostic tests used to detect various diseases [140]. Nanoparticles can be engineered to bind to specific biomarkers in the body that are indicative of disease, allowing for early detection and treatment [140]. In the field of therapeutics, nanotechnology can improve drug delivery systems, enhancing drug efficacy while minimizing side effects. Nanoparticles can be designed to improve drug solubility, stability, and specificity, ensuring that drugs reach their intended targets and remain active for longer periods of time [139,140,141,142].

Additionally, nanotechnology can be used to develop novel vaccines and immunotherapies, as well as new tools for regenerative medicine. For instance, nanoparticles can be used to create scaffolds for tissue engineering and repair, promoting the growth of new tissue and accelerating healing processes [73,85,86]. The use of such small-scale nanomedicine shows a direct impact on public health due to the interconnectedness among humans and animals within the same living environment. The effort is going on to increase meat and milk production, leading to a reduction in vaccine residues and drug resistance problems in veterinary medicine [142,143]. Moreover, this medicinal revolution remains cost-effective and helps to minimize the amount of discarded milk and meat products. In addition to that, in modern pet care, nutritional and hygienic products are also being introduced in the market under the genesis of successful practices in nanotechnology [143]. Overall, nanotechnology offers exciting possibilities for improving animal health and welfare and has the potential to revolutionize veterinary medicine.

Nanosensors refer to small devices that can detect and analyze chemical or biological agents at the molecular level. They have various applications, including monitoring air quality and detecting pathogens in food and water [12]. Nano-microbivors, on the other hand, are small (microscopic) organisms that can consume or break down contaminants such as organic chemicals and heavy metals in the environment [17]. They can be used for bioremediation purposes and for treating contaminated soil and groundwater [144,145]. There is an interlink between these concepts, in that nanosensors and nano-microbivors can be used in the detection and remediation of chemical warfare agents [146]. For example, nanosensors can be developed to detect the presence of chemical warfare agents in air or water, while nano-microbivors can be used to break down or detoxify these agents in the environment [146,147]. In this way, these technologies are important tools in ensuring national and global security.

A new wave of nanosensors is being developed to be utilized for military purposes against detection of airborne and released chemical agents that could be easily exhaled and inhaled with toxic outcomes [12,17]. Phagocytes have a cellular clearing digestive function; based on this principle, artificially designed nanoscale microbiomes are being used in studies to clean the bloodstream by digesting toxic pathogens [146]. They perform this function in a very limited time as compared to other medication options without causing any toxicity or septic shock conditions. A similar principle of action will be utilized to detect the amount of inhaled prohibited drugs such as marijuana, banned substances, and alcohol concentrations in individuals, against which the use of such substances is strictly prohibited in patients [148]. Such advanced technologies may take the place of traditional procedures, which are extensive and time-consuming diagnostic procedures.

During the COVID-19 pandemic, nanomedicine has played a crucial role in developing diagnostic tools, treatment strategies, and vaccine delivery methods. The link between the coronavirus and nanoparticles based on size and function is relatively straightforward. In terms of size, both the virus particles and nanoparticles are tiny particles with a size on the nanoscale [149]. This small size allows them to interact with each other on a very tiny scale. Similarly, in terms of functional similarities, nanoparticles can be engineered or designed to have specific functions. For example, some nanoparticles can be coated with molecules that make them stick to viruses such as the coronavirus [150]. This function is essential because it allows nanoparticles to grab onto the virus. Thus, in the context of the coronavirus, scientists have explored how nanoparticles can be used in various ways including detection, treatment, and protective responses. Nanoparticles can be designed to bind to specific parts of the coronavirus. When they attach to the virus, they can change color or emit light, making it easier for scientists and doctors to detect the presence of the virus in a sample, such as a patients blood or saliva [151]. Similarly, nanoparticles can also be used to deliver medicines directly to the virus or infected cells. Think of nanoparticles as tiny delivery vehicles that can carry antiviral drugs right to the site of infection, potentially making treatments more effective [152]. In addition, regarding the protective technologies against COVID-19, Some masks and face coverings have been designed with nanoparticle coatings that can trap and neutralize viruses, including the coronavirus, when they come into contact with the masks surface [149,151]. Furthermore, nanoparticles have been used to create highly sensitive and specific diagnostic tests that can detect SARS-CoV-2 in patient samples [149]. Nanoparticles have also been used to develop therapeutics that can directly target the virus, as well as improve the delivery and efficacy of existing drugs [149].

In addition, nanotechnology has been used to improve the stability and efficacy of vaccines, as well as develop new delivery methods such as nasal sprays and microneedle patches [149,150]. These approaches can help increase vaccine accessibility and effectiveness, particularly in resource-limited settings. The breakthrough and rapid responses coming from nanomedicine can be ascertained by the fact that nanotechnology is also being utilized for vaccine drug manufacturing technologies against COVID-19 [151]. Since nanomedicine has already proven its benefits for disease diagnosis, treatment, and prevention, it is being employed to tackle the pandemic. Now, nano-based technology is on hand and is being considered for utilization in manufacturing antiviral technology to integrate into personalized medical equipment and to manufacture nano-based drugs [150,151]. The sole purpose is the greater safety of medical workers and to save patients suffering from the impediments of the coronavirus with more sensitive medicine and machinery.

In this regard nanomaterials, such as quantum dots, are being introduced into biosensors for diagnostics experiments and other nanoassemblies, such as liposomes, polymeric and lipid nanoparticles, metallic nanoparticles, and micelles, which are being utilized for antiviral drug encapsulation and drug conjugation [150,151,152,153]. The great benefit would be increased pharmacological impact and more efficient drug targeting. Studies are showing that these antiviral properties of nanoparticles function by blocking the binding, entry, and replication of coronavirus in the body [154]. With this technology, the toxicity linked to normal body cells owing to nanoparticle application is the major factor of concern and thus needs to be investigated and improved for future applications [155]. Overall, nanomedicine holds great promise in the fight against COVID-19 and could potentially revolutionize the way we diagnose, treat, and prevent infectious diseases in the future. below shows the link between nanoparticles and coronavirus in terms of the chemistry of the structure, size, and functionality that could be used as an exemplary overview as to how nanotechnology could be majorly utilized to discover antiviral treatments in the future. Commercial applications of nanotechnology in medical field are summarized in .

A link between coronavirus and nanoparticles based on size and function.

Examples of nanotechnological applications and their commercialization in the medical field.

The side effects of nanotechnology are of great concern for humans, animals, and the overall environment. While the toxicity attached to these assemblies is poorly understood, the scientific community remains unsure as to what level they can extend the applications of nanotechnology, especially in medicine, which is quite a sensitive domain of healthcare [142]. In previous years, some nano-based products were introduced but later pulled back from the market owing to the reported side effects in the general public. The risk assessment of nanomedicine is thus a critical topic and needs to be assessed soon [145].

The need is to prioritize experiments for nanoparticle safety, dosing adjustment, and usage. The miracles of nanotechnology itself can be used in sensors and markers for biological, chemical, and environmental remediations [162]. Toxicity profiling of consumer products should be specifically carried out. Skin care and dental products containing different nanomaterial liposomes, cubosomes, solid lipid nanoparticles, and dendrimers must be specifically assessed, and their side effects must be determined so that more modified, effective, and harmless nanoemulsions can be introduced and utilized in the future [163].

Similarly, the issue of bioaccumulation and persistence is attached to nanotechnology. Nanomaterials have the potential to persist in the environment for extended periods and accumulate in living organisms [162,163,164]. This can lead to potentially adverse effects on both human health and ecosystems. Additionally, in healthcare settings, medical professionals who handle nanomaterials may be at risk of potential exposure through inhalation, dermal contact, or ingestion. Safe handling practices and adequate protective measures must be implemented to minimize exposure risks [165]. Moreover, the use of nanomaterials in medical applications also raises ethical considerations regarding informed consent, privacy, equity of access, and potential impacts on vulnerable populations. There is a need to address these ethical concerns to ensure the fair and responsible use of nanomaterials in healthcare [166].

To ensure the safe and sustainable use of nanomaterials in the medical field, several measures can be implemented, such as rigorous and comprehensive risk assessments, which should be conducted to evaluate the potential hazards and risks associated with specific nanomaterials before their deployment in medical applications. Similarly, adequate regulatory frameworks should be in place to ensure the safe production, handling, and utilization of nanomaterials [142,166]. This includes the evaluation of their safety, labeling requirements, and monitoring of their effects in healthcare settings. Additionally, standardized testing methods should be developed to assess the safety and efficacy of nanomaterials for medical use. This includes standardized protocols for toxicity testing, characterization, and quality control. Furthermore, strict control measures should be implemented to minimize occupational exposure to nanomaterials [165]. This includes the use of engineering controls, personal protective equipment, and employee training programs. Moreover, transparent communication about the potential risks and benefits associated with nanomaterials is essential for establishing trust among stakeholders, including healthcare professionals, patients, and the general public [165,166].

The need is to prioritize experiments for nanoparticle safety, dosing adjustment, and usage. The miracles of nanotechnology itself can be used to produce sensors and markers for biological, chemical, and environmental remediations [166]. Toxicity profiling of consumer products should be specifically carried out. Skin care and dental products containing different nonmaterial liposomes, cubosomes, solid lipid nanoparticles, and dendrimers must be specifically assessed, and their side effects must be determined so that more modified, effective, and harmless nano-emulsions can be introduced and utilized in the future [145,166]. Overall, by evaluating potential risks, implementing appropriate regulatory measures, and promoting responsible use, nanomaterials can be safely and sustainably utilized in the medical field for improved diagnostics, drug delivery, and disease treatment.

Nanomaterials hold significant promise for various biomedical advancements and industrial applications. However, their unique physicochemical properties raise concerns about their potential impact on human health and the environment. In order for medical nanomaterials to enter the market, there are many obstacles to overcome, such as FDA certifications and permits, as well as safety and ethical concerns. In recent years, regulatory bodies worldwide have focused on developing appropriate frameworks to ensure the safe and responsible use of nanomaterials. Such an issue should be addressed more intensively in the coming years of nanotech research. Review papers, in this regard, should aim to provide researchers, policymakers, and industry professionals with a comprehensive understanding of the recent regulatory affairs surrounding nanomaterials. By critically examining the current state of nanomaterial regulation, this paper highlights the need for harmonization and collaboration among regulatory agencies worldwide. Regulating industrialization affairs surrounding nanomaterials in medical sciences involves several steps. It is important to note that these steps provide a general framework, but the specific details and processes may vary depending on the jurisdiction and specific requirements of each country or region. A general outline of the process is provided in a table format () below. Steps needed to regulate the industrial affairs of nanotechnology are shown in .

FDA approved and commercialized nanomedicines.

Steps needed to regulate industrialization affairs surrounding nanomaterials in the medical sciences.

A comprehensive search strategy was adopted for this systematic review to include data from diverse, recent, and the most cited sources of study.

Data were collected via a systematic literature search through various online sources including Google Scholar, PubMed, NIH (National Library of Medicine), Web of Science, European database, Springer, and Embase databases. Since the study was focused on the applications of nanotechnology in medicine and healthcare, the major research items were nanotechnology, nanobiotechnology, nanomedicine, nanotechnology and medical applications, nanotechnology and diagnosis, nanotechnology and treatment, nanotechnology and drug-delivery, and nanotechnology and healthcare and esthetics, among other similar search terms. After a thorough analysis of titles and abstracts of publications related to applications of nanotechnology in the medical and healthcare industry, the data was selected to be part of this study. Only studies published in the English language were included in this study. Moreover, only data from 2010 onwards were included in the article.

Multiple types of sources were used, including data from research articles, book chapters, review articles, case reports, clinical trials, and case studies published starting beginning in 2010. Studies with incomplete citations and published before 2010 were excluded from the study.

The future of nanotechnology in healthcare and medicine holds immense potential for revolutionizing the way we diagnose, treat, and prevent diseases. Nanotechnology involves the manipulation of materials at such a small scale where the properties of materials significantly differ from their bulk counterparts, allowing for precise control of their physical, chemical, and biological properties. This opens up new opportunities for developing novel therapies, targeted drug delivery systems, and sensitive diagnostic tools. In addition to drug delivery, targeted delivery, improved drugs, limited dosages, and reduced systematic side effects, nanoparticles can also be used to enhance the efficacy of existing drugs by improving their solubility, stability, and bioavailability. Additionally, nanotechnology-based sensors and devices can monitor patient health in real-time, enabling early detection and personalized treatment plans. In the future, nanotechnology may even enable the development of nanorobots that can navigate through the bloodstream to target and destroy cancer cells or deliver payloads of drugs to particular tissues.

The broad spectrum of nanomedicine covered in this article may be lacking in various other aspects of nanomedicine still in the research pipeline. The vision of nanotechnology might seem heretic and abstract, similar to the in silico experimentation and computational bioinformatics field that was criticized a few years back. However, the field of nanobiotechnology is rapidly appearing as a cutting-edge technology of the 21st century, with diverse implications in science and technology. The theoretical knowledge is there, and applied research is ongoing to make it more progressive. It is predicted that soon, nanotechnology will not remain an option but rather be compulsory in the medical industry. As soon as the cost associated with technology becomes accessible, it is predicted to affect our dentistry, healthcare, and human life more profoundly than in the past. The major need is to curtail the toxicological concerns and risks that are attached to high doses and the excessive use of nanomaterials in drug and treatment regimes. This is important if scientists want to enable the successful operation of nanotechnology in medicine. Overall, the future of nanotechnology in healthcare and medicine holds great promise for improving patient outcomes and revolutionizing the way we approach disease prevention and treatment.

Conceptualization, S.M., K.M. and Y.W.; methodology, S.M., K.M. and Y.W.; validation, S.M., K.M. and Y.W.; formal analysis, S.M., K.M. and Y.W.; resources, K.M. and Y.W.; data curation, S.M., K.M. and Y.W.; writingoriginal draft preparation, S.M., K.M. and Y.W.; writingreview and editing, S.M., K.M. and Y.W.; supervision, Y.W.; funding acquisition, K.M. All authors have read and agreed to the published version of the manuscript.

The rest is here:
Emerging Applications of Nanotechnology in Healthcare and Medicine

While topically-applied medications do help alleviate various skin conditions, they would be even more effective if they could better penetrate the skin's surface. Newly developed nanoceramic "stars" may one day help, by poking tiny holes in the skin.

When medications are applied to the skin in the form of a lotion, the drug molecules are often large enough that they have difficulty passing through the skin's outer layer, called the epidermis. As a result, only a relatively small dosage is delivered beneath the skin's surface.

One possible alternative involves utilizing what are known as microneedle patches. These typically consist of a small square of material with an array of tiny, sharp stud-like needles on its underside.

Made of biocompatible substances such as silk, the needles are loaded with medication, and they painlessly pierce the epidermis when the patch is pressed against the skin. They then dissolve, harmlessly releasing the medication into the interstitial fluid between the skin cells.

When it comes to treating skin maladies, however, microneedle patches have a couple of drawbacks as compared to lotions. For one thing, they're not conducive to treating large areas of skin. For another, they're difficult to apply to nooks and crannies, or any other location that isn't smooth and open.

That's where the nanoceramic stars come in.

They're being developed by Michael Stuer, Patrick Hoffmann and colleagues at Switzerland's Empa research institute, in collaboration with Aldena Therapeutics as part of the StarCURE project.

Empa

Each three-dimensional three-armed star has a diameter of just 0.8 mm, and is currently made of aluminum oxide ceramic material (aka alumina). A laser sintering process was initially used to create each one individually, although the scientists have since produced polymer casting molds which would allow large numbers of the stars to be inexpensively manufactured on a commercial scale.

Batches of the tiny structures are added to a gel, along with a medication. The technology is particularly well-suited to drugs incorporating siRNA (small interfering RNA) molecules.

As the gel is rubbed onto the skin, the sharp-ended stars roll across the epidermis, poking minuscule holes in it. Although those "micro-wounds" close up quickly, they remain open long enough for the medication to get through. The remaining gel is simply wiped off a few seconds after application.

Because the holes don't reach down to the nerve endings, use of the nanoceramic stars is reportedly painless Stuer describes it as feeling like a skin scrub. In fact, he suggests that the technology could also be utilized as an alternative to painful hypodermic needles for administering drugs intravenously.

The scientists are now exploring methods of making the stars biodegradable.

Source: Empa

Continue reading here:
Tiny skin-stabbing stars designed to get meds through the epidermis

Heath JR, Davis ME. Nanotechnology and cancer. Annu Rev Med. 2008;59:251. https://doi.org/10.1146/annurev.med.59.061506.185523.

Article CAS PubMed PubMed Central Google Scholar

Mamo T, Moseman EA, Kolishetti N, Salvador-Morales C, Shi J, Kuritzkes DR, Farokhzad. O. C. Emerging nanotechnology approaches for HIV/AIDS treatment and prevention. Nanomedicine. 2010;5(2):26985. https://doi.org/10.2217/nnm.10.1.

Article CAS PubMed Google Scholar

Pradhan D, Biswasroy P, Goyal A, Ghosh G, Rath G. Recent advancement in nanotechnology-based drug delivery system against viral infections. AAPS PharmSciTech. 2021;22(1):119. https://doi.org/10.1208/s12249-020-01908-5.

Article CAS Google Scholar

Farokhzad OC. Nanotechnology for drug delivery: the perfect partnership. Expert Opin Drug Deliv. 2008;5(9):9279. https://doi.org/10.1517/17425247.5.9.927.

Article CAS PubMed Google Scholar

Shi J, Votruba AR, Farokhzad OC, Langer R. Nanotechnology in drug delivery and tissue engineering: from discovery to applications. Nano Lett. 2010;10(9):322330. https://doi.org/10.1021/nl102184c.

Article CAS PubMed PubMed Central Google Scholar

Sepulveda-Crespo D, Gomez R, De La Mata FJ, Jimenez JL, Muoz-Fernndez M. . Polyanionic carbosilane dendrimer-conjugated antiviral drugs as efficient microbicides: Recent trends and developments in HIV treatment/therapy. Nanomedicine: Nanotechnology, Biology and Medicine. 2015;11(6):14811498. https://doi.org/10.1016/j.nano.2015.03.008

Nachega, J.B., Musoke P., Kilmarx, P.H., Gandhi, M., Grinsztejn, B., Pozniak, A., Rawat, A., Wilson, L., Mills, E.J., Altice, F.L., Mellors, J.W. Global HIV control: is the glass half empty or half full? The Lancet HIV. 2023; 10(9): 617622.

Cooper, D. A., Heera, J., Ive, P., Botes, M., Dejesus, E., Burnside, R., van Der Ryst, E. Efficacy and safety of maraviroc vs. efavirenz in treatment-naive patients with HIV-1: 5-year findings. AIDS (London, England). 2014;28(5):717. https://doi.org/10.1097/QAD.0000000000000131

Vacas-Cordoba E, Galan M, de la Mata FJ, Gomez R, Pion M, Muoz-Fernndez M. . Enhanced activity of carbosilane dendrimers against HIV when combined with reverse transcriptase inhibitor drugs: searching for more potent microbicides. International Journal of Nanomedicine. 2014;9:3591. https://doi.org/10.2147/IJN.S62673

Richman DD, Margolis DM, Delaney M, Greene WC, Hazuda D, Pomerantz RJ. The challenge of finding a cure for HIV infection. Science. 2009;323(5919):13047. https://doi.org/10.1126/science.1165706.

Article CAS PubMed Google Scholar

Yadav P, Bandyopadhyay A, Chakraborty A, Sarkar K. Enhancement of anticancer activity and drug delivery of chitosan-curcumin nanoparticle via molecular docking and simulation analysis. Carbohydr Polym. 2018;182:18898. https://doi.org/10.1016/j.carbpol.2017.10.102.

Article CAS PubMed Google Scholar

Krosch SL. Perceptions and use of complementary and alternative medicine in american Samoa: a survey of health care providers. Hawaii Med J. 2010;69(6 Suppl 3):21.

PubMed PubMed Central Google Scholar

Yim NH, Kim A, Liang C, Cho WK, Ma JY. Guibitang, a traditional herbal medicine, induces apoptotic death in A431 cells by regulating the activities of mitogen-activated protein kinases. BMC Complement Altern Med. 2014;14(1):112. https://doi.org/10.1186/1472-6882-14-344.

Article Google Scholar

Phan QT, Le MH, Le TTH, Tran THH, Xuan PN, Ha PT. Characteristics and cytotoxicity of folate-modified curcumin-loaded PLA-PEG micellar nano systems with various PLA: PEG ratios. Int J Pharm. 2016;507(12):3240. https://doi.org/10.1016/j.ijpharm.2016.05.003.

Article CAS PubMed Google Scholar

El-Moselhy MA, Taye A, Sharkawi SS, El-Sisi SF, Ahmed AF. The antihyperglycemic effect of curcumin in high fat diet fed rats. Role of TNF- and free fatty acids. Food Chem Toxicol. 2011;49(5):112940. https://doi.org/10.1016/j.fct.2011.02.004.

Article CAS PubMed Google Scholar

Srivastava RM, Singh S, Dubey SK, Misra K, Khar A. Immunomodulatory and therapeutic activity of curcumin. Int Immunopharmacol. 2011;11(3):33141. https://doi.org/10.1016/j.intimp.2010.08.014.

Article CAS PubMed Google Scholar

Aggarwal BB, Sundaram C, Malani N, Ichikawa H. Curcumin: the Indian solid gold. Mol Targets Therapeutic uses Curcumin Health Disease. 2007;175. https://doi.org/10.1007/978-0-387-46401-5_1.

Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Mol Pharm. 2007;4(6):80718. https://doi.org/10.1021/mp700113r.

Article CAS PubMed Google Scholar

Jger R, Lowery RP, Calvanese AV, Joy JM, Purpura M, Wilson JM. Comparative absorption of curcumin formulations. Nutr J. 2014;13(1):18. https://doi.org/10.1186/1475-2891-13-11.

Article CAS Google Scholar

Basniwal RK, Buttar HS, Jain VK, Jain N. Curcumin nanoparticles: preparation, characterization, and antimicrobial study. J Agric Food Chem. 2011;59(5):205661. https://doi.org/10.1021/jf104402t.

Article CAS PubMed Google Scholar

Wang D, Veena MS, Stevenson K, Tang C, Ho B, Suh JD, Wang MB. Liposome-encapsulated curcumin suppresses growth of head and neck squamous cell carcinoma in vitro and in xenografts through the inhibition of nuclear factor B by an AKT-independent pathway. Clin Cancer Res. 2008;14(19):622836. https://doi.org/10.1158/1078-0432.CCR-07-5177.

Article CAS PubMed Google Scholar

Gupta V, Aseh A, Ros CN, Aggarwal BB, Mathur AB. Fabrication and characterization of silk fibroin-derived curcumin nanoparticles for cancer therapy. Int J Nanomed. 2009;4:115. https://doi.org/10.2147/ijn.s5581.

Article CAS Google Scholar

Das RK, Kasoju N, Bora U. Encapsulation of curcumin in alginate-chitosan-pluronic composite nanoparticles for delivery to cancer cells. Nanomed Nanotechnol Biol Med. 2010;6(1):15360. https://doi.org/10.1016/j.nano.2009.05.009.

Article CAS Google Scholar

Maiti K, Mukherjee K, Gantait A, Saha BP, Mukherjee PK. Curcuminphospholipid complex: preparation, therapeutic evaluation and pharmacokinetic study in rats. Int J Pharm. 2007;330(12):15563. https://doi.org/10.1016/j.ijpharm.2006.09.025.

Article CAS PubMed Google Scholar

Yallapu MM, Ebeling MC, Chauhan N, Jaggi M, Chauhan SC. Interaction of curcumin nanoformulations with human plasma proteins and erythrocytes. Int J Nanomed. 2011;6:2779. https://doi.org/10.2147/IJN.S25534.

Article CAS Google Scholar

Dezfouli EA, Kiaie SH, Danafar H, Nomani A, Sadeghizadeh M. BTN-PEG-PCL nanoparticles for targeted delivery of curcumin: in vitro and in Ovo assessment. J Drug Deliv Sci Technol. 2022;74:103382. https://doi.org/10.1016/j.jddst.2022.103382.

Article CAS Google Scholar

Reddy AS, Lakshmi BA, Kim S, Kim J. Synthesis and characterization of acetyl curcumin-loaded core/shell liposome nanoparticles via an electrospray process for drug delivery, and theranostic applications. Eur J Pharm Biopharm. 2019;142:51830. https://doi.org/10.1016/j.ejpb.2019.07.024.

Article CAS PubMed Google Scholar

Cheng YH, Ko YC, Chang YF, Huang SH, Liu CJ. L. Thermosensitive chitosan-gelatin-based hydrogel containing curcumin-loaded nanoparticles and latanoprost as a dual-drug delivery system for glaucoma treatment. Exp Eye Res. 2019;179:17987. https://doi.org/10.1016/j.exer.2018.11.017.

Article CAS PubMed Google Scholar

Gao M, Long X, Du J, Teng M, Zhang W, Wang Y, Li J. Enhanced curcumin solubility and antibacterial activity by encapsulation in PLGA oily core nanocapsules. Food Funct. 2020;11(1):44855. https://doi.org/10.1039/C9FO00901A.

Article CAS PubMed Google Scholar

Ayubi M, Karimi M, Abdpour S, Rostamizadeh K, Parsa M, Zamani M, Saedi A. Magnetic nanoparticles decorated with PEGylated curcumin as dual targeted drug delivery: synthesis, toxicity and biocompatibility study. Mater Sci Engineering: C. 2019;104:109810. https://doi.org/10.1016/j.msec.2019.109810.

Article CAS Google Scholar

Lian, T., Peng, M., Vermorken, A. J., Jin, Y., Luo, Z., Van de Ven, W. J., Cui,Y. Synthesis and characterization of curcumin-functionalized HP--CD-modified GoldMag nanoparticles as drug delivery agents. Journal of nanoscience and nanotechnology. 2016;16(6):62586264. https://doi.org/10.1166/jnn.2016.11370.

Bisht S, Feldmann G, Soni S, Ravi R, Karikar C, Maitra A, Maitra A. Polymeric nanoparticle-encapsulated curcumin (nanocurcumin): a novel strategy for human cancer therapy. J Nanobiotechnol. 2007;5(1):118. https://doi.org/10.1186/1477-3155-5-3.

Article CAS Google Scholar

Chen Y, Wu Q, Zhang Z, Yuan L, Liu X, Zhou L. Preparation of curcumin-loaded liposomes and evaluation of their skin permeation and pharmacodynamics. Molecules. 2012;17(5):597287. https://doi.org/10.3390/molecules17055972.

Article CAS PubMed PubMed Central Google Scholar

Mulik RS, Mnkknen J, Juvonen RO, Mahadik KR, Paradkar AR. Transferrin mediated solid lipid nanoparticles containing curcumin: enhanced in vitro anticancer activity by induction of apoptosis. Int J Pharm. 2010;398(12):190203. https://doi.org/10.1016/j.ijpharm.2010.07.021.

Article CAS PubMed Google Scholar

Falconieri MC, Adamo M, Monasterolo C, Bergonzi MC, Coronnello M, Bilia AR. New dendrimer-based nanoparticles enhance curcumin solubility. Planta Med. 2017;83(05):4205. https://doi.org/10.1055/s-0042-103161.

Article CAS PubMed Google Scholar

Babaei E, Sadeghizadeh M, Hassan ZM, Feizi MAH, Najafi F, Hashemi SM. Dendrosomal curcumin significantly suppresses cancer cell proliferation in vitro and in vivo. Int Immunopharmacol. 2012;12(1):22634. https://doi.org/10.1016/j.intimp.2011.11.015.

Article CAS PubMed Google Scholar

Mirgani MT, Isacchi B, Sadeghizadeh M, Marra F, Bilia AR, Mowla SJ, Babaei E. Dendrosomal curcumin nanoformulation downregulates pluripotency genes via miR-145 activation in U87MG glioblastoma cells. Int J Nanomed. 2014;9:403. https://doi.org/10.2147/IJN.S48136.

Article CAS Google Scholar

Jain K, Kesharwani P, Gupta U, Jain NK. Dendrimer toxicity: Lets meet the challenge. Int J Pharm. 2010;394(12):12242. https://doi.org/10.1016/j.ijpharm.2010.04.027.

Article CAS PubMed Google Scholar

DEmanuele A, Attwood D. Dendrimerdrug interactions. Adv Drug Deliv Rev. 2005;57(15):214762. https://doi.org/10.1016/j.addr.2005.09.012.

Article CAS PubMed Google Scholar

Markatou E, Gionis V, Chryssikos GD, Hatziantoniou S, Georgopoulos A, Demetzos C. Molecular interactions between dimethoxycurcumin and pamam dendrimer carriers. Int J Pharm. 2007;339(12):2316. https://doi.org/10.1016/j.ijpharm.2007.02.037.

Article CAS PubMed Google Scholar

Aulenta F, Hayes W, Rannard S. Dendrimers: a new class of nanoscopic containers and delivery devices. Eur Polymer J. 2003;39(9):174171. https://doi.org/10.1016/S0014-3057(03)00100-9.

Article CAS Google Scholar

Agrawal P, Gupta U, Jain NK. Glycoconjugated peptide dendrimers-based nanoparticulate system for the delivery of chloroquine phosphate. Biomaterials. 2007;28(22):334959. https://doi.org/10.1016/j.biomaterials.2007.04.004.

Article CAS PubMed Google Scholar

Namazi H, Adeli M. Novel linearglobular thermoreversible hydrogel ABA type copolymers from dendritic citric acid as the A blocks and poly (ethyleneglycol) as the B block. Eur Polymer J. 2003;39(7):1491500. https://doi.org/10.1016/S0014-3057(02)00385-3.

Article CAS Google Scholar

Namazi H, Adeli M. Dendrimers of citric acid and poly (ethylene glycol) as the new drug-delivery agents. Biomaterials. 2005;26(10):117583. https://doi.org/10.1016/j.biomaterials.2004.04.014.

Article CAS PubMed Google Scholar

Haririan I, Alavidjeh MS, Khorramizadeh MR, Ardestani MS, Ghane ZZ, Namazi H. Anionic linear-globular dendrimer-cis-platinum (II) conjugates promote cytotoxicity in vitro against different cancer cell lines. Int J Nanomed. 2010;5:63. https://doi.org/10.2147/ijn.s8595.

Article CAS Google Scholar

Alavidjeh MS, Haririan I, Khorramizadeh MR, Ghane ZZ, Ardestani MS, Namazi H. Anionic linear-globular dendrimers: biocompatible hybrid materials with potential uses in nanomedicine. J Mater Science: Mater Med. 2010;21(4):112133. https://doi.org/10.1007/s10856-009-3978-8.

Article CAS Google Scholar

Zabihollahi R, Sadat S, Vahabpour R, Aghasadegh M, Memarnejadian A, Ghazanfari T, Azadmanesh K. Development of single-cycle replicable human immunodeficiency virus 1 mutants. Acta Virol. 2011;55(1). https://doi.org/10.4149/av_2011_01_15.

Rezaei A, Zabihollahi R, SALEHI M, Moghim SH, Yazdanpanahi TAMIZIFH, N., Amini G. Designing a non-virulent HIV-1 strain: potential implications for vaccine and experimental research. J Res Med Sci. 2007;12(5):22734.

CAS Google Scholar

Boas U, Heegaard PM. Dendrimers in drug research. Chem Soc Rev. 2004;33(1):4363. https://doi.org/10.1039/B309043B.

Article CAS PubMed Google Scholar

Mohanty C, Sahoo SK. The in vitro stability and in vivo pharmacokinetics of curcumin prepared as an aqueous nanoparticulate formulation. Biomaterials. 2010;31(25):6597611.

Article CAS PubMed Google Scholar

Erfani-Moghadam V, Nomani A, Zamani M, Yazdani Y, Najafi F, Sadeghizadeh M. A novel diblock of copolymer of (monomethoxy poly [ethylene glycol]-oleate) with a small hydrophobic fraction to make stable micelles/polymersomes for curcumin delivery to cancer cells. Int J Nanomed. 2014; 554154.

Phan QT, Le MH, Le TTH, Tran THH, Xuan PN, Ha PT. Characteristics and cytotoxicity of folate-modified curcumin-loaded PLA-PEG micellar nano systems with various PLA: PEG ratios. Int J Pharm. 2016;507(12):3240.

Article CAS PubMed Google Scholar

Waghela BN, Sharma A, Dhumale S, Pandey SM, Pathak C. Curcumin conjugated with PLGA potentiates sustainability, anti-proliferative activity and apoptosis in human colon carcinoma cells. PLoS ONE. 2015; 10(2), e0117526.

Dolai S, Shi W, Corbo C, Sun C, Averick S, Obeysekera D, Raja K. Clickedsugarcurcumin conjugate: modulator of amyloid- and tau peptide aggregation at ultralow concentrations. ACS Chem Neurosci. 2011;2(12):6949. https://doi.org/10.1021/cn200088r.

Article CAS PubMed PubMed Central Google Scholar

Safavy A, Raisch KP, Mantena S, Sanford LL, Sham SW, Krishna NR, Bonner JA. Design and development of water-soluble curcumin conjugates as potential anticancer agents. J Med Chem. 2007;50(24):62848. https://doi.org/10.1021/jm700988f.

The rest is here:
Inhibition of HIV-1 infection with curcumin conjugated PEG-citrate ...

Date Established: February 26, 1867 Date Organized: Location: County Seat: Independence Origin of Name: In honor of Gen. Richard Montgomery (1738-1775), a Revolutionary War hero who led the army into Canada, capturing the city of Montreal; he died while attempting to capture Quebec. Cities & Townships PlacePopulation (2020 census) Caney (city) 1,788 Caney Township 1,134 Cherokee Township 415 Cherry Township 462 Cherryvale (city) 2,192 Coffeyville (city) 8,826 Drum Creek Township 494 Fawn Creek Township 1,857 Independence (city) 8,548 Independence Township 2,241 Liberty Township 511 Louisburg Township 552 Parker Township 1,077 Rutland Township 299 Sycamore Township 805 West Cherry Township 285 Total population: 31,486 Population: 1870 (7,564) 1880 (18,213) 1890 (23,104) 1900 (29,039) 1910 (49,474) 1920 (49,645) 1930 (51,411) 1940 (49,729) 1950 (46,487) 1960 (45,007) 1970 (39,949) 1980 (42,281) 1990 (38,816) 2000 (36,252) 2010 (35,471) 2020 (31,486) Other Resources: Post offices in Montgomery CountyCemeteries in Montgomery County, As of 1906Newspapers Available on MicrofilmTownships and Independent Cities in Montgomery CountyBibliographyKansas Memory Links to Other Sites: Montgomery County GenWebEarly Kansas Maps [KanColl] Look for other counties:

Excerpt from:
Montgomery County, Kansas - Kansas Historical Society

P T. 2012 Sep; 37(9): 512-517, 525.

Part 1: Emerging Concepts

The author is a Consultant Medical Writer living in New Jersey.

Nanoparticles may soon be used to transport diagnostic and therapeutic drugs to targeted sites not normally accessible, thereby improving treatment and reducing costs. Further research is still needed to establish the efficacy and safety of these nanomaterials.

This is the first in a series of three articles about nanomedicine. Part 2 will discuss the current and future clinical applications of nanomedicine. The third article in this series will focus on the regulatory and safety challenges presented by nanomedicine.

Nanomedicine, the application of nanotechnology to medicine, is currently at an early stage but it is expected to have a revolutionary impact on health care.1 Nanomedical research is heavily supported by public policy and investment, and is progressing rapidly.1,2 The continued development of nanomedicines has the potential to provide numerous benefits, including improved efficacy, bioavailability, doseresponse, targeting ability, personalization, and safety compared to conventional medicines.25 The most exciting concept in nanomedical research may be the design and development of multifunctional nanoparticle (NP) complexes that can simultaneously deliver diagnostic and therapeutic agents to targeted sites.5,6 These capabilities are unprecedented and represent tremendous progress toward improving patient diagnosis, treatment, and follow-up.6 However, despite these potential benefits, essential data regarding the pharmacokinetics, pharmacodynamics, and toxicity of many nanomaterials are currently lacking.5,7

Nanotechnology is a rapidly advancing field that is expected to have a revolutionary impact on many industries, including medicine.8,9 Nanotechnology has been made possible through the convergence of many scientific fields, including chemistry, biology, physics, mathematics, and engineering.1,2,9

A nanometer (nm) is one billionth of a meter, and the prefix nano- comes from the Greek word for dwarf.4,10 Nanotechnology provides scientists with new tools for the investigation, manipulation, and control of atoms, molecules, and submicroscopic objects, generally ranging from 1 to 100 nm.1,6 Nanotechnology allows scientists to take advantage of naturally occurring quantum effects at the nanoscale level that influence biological, physical, chemical, mechanical, and optical properties.6,10,11 These unique effects often give nanoscale materials desirable chemical, physical, and biological properties that differ from those of their larger, or bulk, counterparts.12

The convergence of nanotechnology and medicine has led to the interdisciplinary field of nanomedicine.6 Advances in genetics, proteomics, molecular and cellular biology, material science, and bioengineering have all contributed to this developing field, which deals with physiological processes on the nanoscale level.6,9 Many of the inner workings of a cell naturally occur on the nanoscale level, since the dimensions of many biologically significant molecules like water, glucose, antibodies, proteins, enzymes, receptors, and hemoglobin are already within the nanoscale range (see ).6,11 Many researchers are currently working on medical treatments, devices, and instruments that use nanotechnology to increase efficacy, safety, sensitivity, and personalization.11 Potentially beneficial properties of nanotherapeutics include improved bioavailability, reduced toxicity, greater dose response, and enhanced solubility compared with conventional medicines.2

This scale depicts the relative size of nanoscale, microscopic, and macroscopic objects. (Adapted from the National Cancer Institute.15)

The National Nanotechnology Initiative (NNI), a federal research and development program, defines nanotechnology as the science of materials and phenomena in the range of 1 to 100 nm in diameter.2,4,10 Many federal agencies, including the FDA and the Patent and Trademark Office (PTO), continue to use this definition.2 However, some experts say that this size limitation is artificial and misleading, since nanomaterials can have unique properties even in sizes up to several hundred nanometers.2

The National Institutes of Health (NIH) has presented an alternative definition of nanotechnology that doesnt rely on size; instead, it defines the field as (1) studies that use nanotechnology tools and concepts to study biology, (2) the engineering of biological molecules to have functions that differ from those that they have in nature, or (3) the manipulation of biological systems by methods more precise than standard molecular biological, synthetic, chemical, or biochemical approaches.2

Nanotechnology has the potential to be used in a wide range of products, including medicines, electronics, cosmetics, and foods.1,1315 According to the Project for Emerging Nanotechnologies at The Woodrow Wilson International Center for Scholars, more than 800 nanotechnology-based products are already on the market.9 Nanotechnology has been used in laptop computers, cell phones, digital cameras, water-filtration systems, and cosmetics.14,15 Nanotechnology research is also under way to improve the bioavailability of food nutrients and to develop food packaging that detects and prevents spoilage.14,16

Nanotechnology has also been applied to improve a number of medical products and processes;14,15 these include drugs, medical imaging, antimicrobial materials, medical devices, sunscreens, burn and wound dressings, dental-bonding agents, sunscreens, and protective coatings for eyeglasses.14,15 Nanotechnology has improved drug targeting and bioavailability, diagnostic imaging, biomarker detection sensitivity, and drug-delivery efficiency.16 Some nanomedicines that are currently on the market include doxorubicin HCl liposome injection (Doxil, Ortho Biotech) for ovarian cancer; daunorubicin citrate liposome injection (DaunoXome, Diatos) for advanced AIDS-related Kaposis sarcoma; and amphotericin B liposome injection (AmBisome, Gilead) for fungal infections.3,5 In addition, paints containing silver NPs, which have antimicrobial properties, are being used in indoor medical settings, such as in hospitals.17

Nanotechnology is a rapidly growing field. In 2008, nanotechnology was estimated to be a $10.5 billion industry in the U.S, mostly due to consumer product applications.17 It is estimated that the nanotechnology industry will grow to $1 trillion by 2015, representing an increase of about 100-fold in just 7 years.17

Nanomedicine has always been a major application for nanotechnology. 8 According to the National Science Foundation (NSF), by 2020, one-third of patents and start-up companies in the nanotechnology sector will involve biomedical applications. 8,18 The NSF also predicts that nearly half of future pharmaceuticals will have some nanotechnology components.4,18

The physical characteristics of NPs can differ in many ways that influence function.9 A discussion of several of these physical features follows.

NPs are inherently small, with at least one dimension in the range of 1 to 100 nm, although they can also be micrometer (m)-sized particles.6,9 NPs have novel structural, optical, and electronic properties that many larger molecules or bulk solids lack.9 They also have improved solubility, so they may be used to reinvestigate bulk drug counterparts that are known to have poor solubility.6 This property may provide the ability to convert insoluble or poorly soluble drugs into soluble aqueous suspensions, thus eliminating the need for toxic organic solvents.4 Another key benefit related to the small size of NPs is an increased bioavailability and circulation time.3 Studies have shown that particles under 200 nm have longer circulation times, compared with larger particles, irrespective of any surface modifications present.3

NPs come in a variety of shapes, including spheres, discs, hemispheres, cylinders, cones, tubes, and wires.6,9 NPs can also be hollow, porous, or solid.5 These characteristics of NPs can be selected on the basis of interactivity, loading capacity, and transport capabilities.6 For example, a hollow NP may be an attractive carrier for drug therapies or imaging contrast agents.6

One feature of NPs that gives them unique physical properties is a large surface area relative to size.2 As particle size decreases, total surface area increases exponentially ().2,11 An increase in surface area means that a greater proportion of atoms are located on the particle surface relative to the core.2 This phenomenon makes NPs more reactive compared with conventional larger molecules, or bulk solid counterparts.2 Increased surface area is also responsible for the enhanced water solubility and bioavailability that often occur with NPs.2

Illustration depicting the exponential increase in surface area that occurs with nanoscale materials. (Adapted from the National Technology Initiative.11)

The large surface area of NPs also allows them to be designed to include a broad range of surface characteristics, including conjugation with electrostatic charges or biomolecules.6 Such surface features can be strategically selected for targeting and other purposes and are therefore determined on that basis.9

If NPs are properly designed, their small size can enable them to cross physiological barriers to deliver drugs to sites that are not normally accessible by traditional means.6 For example, the increased permeability of an NP may allow it to transport cancer drugs into tumors by passing through neovessel pores that are less than 1 m in diameter.5 The increased permeability of NPs may also allow them to cross the bloodbrain barrier through the use of different uptake mechanisms.6

A wide variety of NPs and materials are used in nanomedicine, depending on the application.6 Among the most widely used are liposomes, polymers, quantum dots (QDs), iron oxide (IO) particles, and carbon nanotubes and nanoshells.6

A liposome is a spherical vesicle composed of a lipid bilayer membrane and an empty core that usually carries an aqueous solution.5 Liposomes are usually 90 to 150 nm in diameter and are thus slightly larger than conventional NPs.5 Liposomes are often designed to carry biomolecules (e.g., monoclonal antibodies, antigens) that are conjugated to the surface as ligands.5

Liposomes are often used in nanomedical research because they have many unique properties.5 The components of liposomes are similar to natural human cell membranes; thus, they confer liposomal drug delivery with several intrinsic benefits.5 Liposomes circulate in the bloodstream for an extended time, compared with non-liposomal drugs, providing a longer treatment effect. Liposomes also accumulate at the site of a tumor or infection, naturally locating and delivering higher drug levels to these targets.5 Liposomes can carry and deliver either hydrophilic or hydrophobic therapies, which can be stored in their empty cores.6 By using lipids of different fatty-acid-chain lengths, scientists can construct liposomes to be temperature-sensitive or pH-sensitive, thereby permitting the controlled release of their contents only when they are exposed to specific environmental conditions.5

In contrast to other materials, data on the safety and efficacy of many polymers already exist; therefore, polymer NPs are widely used in nanomedical research.3 Polymer NPs can be fabricated in a wide range of varieties and sizes, ranging from 10 nm to 1 m.3,5 Some polymer NPs can facilitate drug release for weeks and do not accumulate in the body.3,5,6 As such, polymeric NPs are considered promising carriers for numerous medications, including those used in cancer, cardiovascular disease, and diabetes treatments; bone-healing therapies; and vaccinations.3 Contrast agents can also be conjugated to the surface of polymeric NPs, allowing them to be used in diagnostic imaging.5

Biodegradable polymers are of particular interest, since they can be fully metabolized and removed from the body.6Poly-lactic-co-glycolic acid (PLGA) is an especially intriguing example of a biodegradable polymer, since relative proportions of polylactic acid (PLA) and polyglycolic acid (PGA) can be used to fine-tune the biodegradability of PLGA.6

Quantum dots (QDs) are semiconductor nanocrystals that range in size from 2 to 10 nm and usually consist of 10 to 50 atoms.4,5 Although QDs have been used in electronics and optics for 20 years, they have only recently been applied to nanomedical research.5 The most commonly used QDs for biomedical applications contain cadmium selenide (CdSe) or cadmium telluride (CdTe).4 QDs containing indium phosphide (InP) and indium arsenide (InAs) are also frequently used.4

QDs have unique optical and electronic properties, making them valuable as luminescent probes and giving them tremendous potential in many biomedical applications.4,5 QDs are intrinsically fluorescent and emit light over a broad range, from the near-ultraviolet (UV) to mid-infrared spectrum.9 They have size-dependent optical properties, extraordinary photostability, and surface properties that can be fine-tuned, which make them ideal for optical imaging.4 QDs have molar extinction coefficients that are 10 to 50 times larger than those of organic dyes, making them much brighter in in vivo conditions.5 They have long blood circulation times and can fluoresce for several months in vivo.5

QDs also have sufficient surface area to attach agents for simultaneous targeted drug delivery and in vivo imaging or for tissue engineering.4 Many uses of QDs for in vivo imaging have already been reported, including lymph node and angiogenic vessel mapping and cell subtype isolation.5 QDs are very efficient agents for cancer diagnosis in vivo, because the extremely small size of the QDs allows unimpeded access to systemic circulation and surface modifications can target them to neoplastic sites.4 Additional potential uses for QDs include image-guided surgery, light-activated therapies, and diagnostic tests.19

Surface coatings have been found to enhance the surface fine-tunability and increase the fluorescent yield of QDs.4 They may also reduce the adverse effects that can be elicited by QDs containing Cd, Se, and As, which are toxic materials.4 At present, the investigation of QDs is restricted to in vitro and animal studies because of toxicity concerns regarding these heavy metals.5,19 Novel methods to produce new generations of QDs in which toxic materials are reduced or absent are being pursued for future applications in humans.5

Superparamagnetic NPs, like iron oxide (SPIO) and magnetite, have been used for years as nontargeted contrast agents for magnetic resonance imaging (MRI).1,5,17 However, these NPs do have superparamagnetic properties that allow them to be directed in situ with the use of a magnetic field.17 They also have a long retention time in circulation, are usually biodegradable, and have low toxicity.5 They are therefore excellent candidates for producing imageable therapeutic nanodevices.5

In addition to possessing other desirable properties, SPIO NPs can also be functionalized (designed) to achieve specific tumor targeting.5 SPIO NPs are increasingly being used for the development of target-specific MRI contrast agents.5 To date, SPIO NPs have been used for many applications, such as the delivery of antibiotics and drugs with simultaneous enhancement of MRI contrast and for the separation of bacteria from biomolecules.17

Carbon nanotubes are composed of a distinct molecular form of carbon atoms that give them unusual thermal, mechanical, and electrical properties.5 For example, they are 100 times stronger than six times their weight in steel.5 Carbon nanotubes modified with polyethylene glycol (PEG) are surprisingly stable in vivo, with long circulation times and low uptake by the reticuloendothelial system (RES).5 Carbon nanotubes have been used for the delivery of imaging and therapeutic agents and in the transport of DNA molecules into cells.5 The nanoscale dimensions of single-walled and multiwalled carbon nanotubes, along with their electrocatalytic properties and high surface area, have compelled researchers to utilize them as nanoelectrodes.20

Carbon nanoshells are composed of a silica core that is covered by a thin metallic shell, usually composed of gold.5 Carbon nanoshells have an ability to scatter light, a feature that is useful for cancer imaging.5 However, their primary use continues to be in thermal ablation therapy.5 Alternatively, focused lasers have been useful for cancer thermotherapy, but they cannot discriminate between diseased and healthy tissue.1 However, when carbon nanoshells are used for targeting in thermal ablation therapy, thermal energy passes through healthy tissue without causing harm, killing only the targeted tumor cells.5 In mice, carbon nanoshells and near-infrared spectroscopy (NIRS) thermal ablation therapy completely eliminated colon carcinoma cell tumors in vivo.5

The aforementioned, and other, NPs are used to construct multifunctional NP complexes that mix and match different features, or functionalizations, in order to achieve an intended purpose.17 A multifunctional NP complex may be designed to include the following components ():3,5,21

surface ligands that target the attachment of NPs to specific locations (e.g., organs, cells, or tissues).

linker molecules that release the cargo carried by the NP at the target site in response to a remote trigger or specific environmental cues.

a core that encapsulates targeting or imaging cargo or has optical or magnetic properties (gold, SPIO) that can localize the NP at the target site.

one or more therapeutic or diagnostic cargoes that are encapsulated in the NP core or attached to its surface.

a coating, such as PEG, that improves biocompatibility and/or enhances bioavailability by increasing circulation times and slowing clearance from the body.

Diagram representing a multifunctional NP complex. The carrier particle, payload, and surface modifiers can be customized. PEG = polyethylene glycol. (Adapted from Ferrari M. Nat Rev Cancer 2005;5[3]:161171.21)

One of the most interesting capabilities in nanomedicine is the functionalization of NPs.7 Functionalization involves altering properties of an NP through chemical or physical modifications that are applied to achieve a desired effect.7 This process can provide local or directed delivery, prolong drug effects, facilitate transport into target cells, locate a tumor or area of infection, provide feedback regarding efficacy or drug delivery, or reduce blood flow shear effects.9 A discussion of the various approaches to functionalizing NPs follows.

NPs can be administered locally or can be actively targeted using cell-specific ligands, magnetic localization, and/or size-based selectivity.3 Many factors need to be considered when constructing targeted NPs, including size, biocompatibility, target affinity, avoidance of the RES, and stability in the blood, as well as the ability to facilitate controlled drug release.7

Magnetic polymer nanocomposites or magnetoliposomes grafted with drug molecules have great potential for targeted drug delivery.3 These NPs have potentially favorable biodistribution and pharmacokinetic profiles, which can be enhanced by the external application of a static magnetic field at the site of action.3 For example, in one study, MRI confirmed that magnetic NPs had migrated toward neodymium/iron/boron (NdFeB) magnets that had been placed outside the peritoneal cavity, above grafts of a human ovarian carcinoma.3

NPs can be engineered to incorporate a wide variety of chemotherapeutic agents that can be targeted directly and specifically to the tumor site for better efficacy and safety.4 NPs can also be filled with contrast agents for imaging purposes.6 In comparison to small-molecule contrast agents, multifunctional NP complexes or NPs used in diagnostic imaging have the advantage of a large surface area that allows targeting through surface modifications and the ability to simultaneously deliver therapeutic agents.1

One way in which NPs can be functionalized for specific applications is through surface conjugation.17 Nanoparticle surfaces can be conjugated with a wide range of diagnostic or therapeutic agents.1 Some candidate biomolecules for NP surface conjugation are cell-penetrating peptides (CPPs) that enhance intracellular delivery, fluorescent dyes for imaging, and agents for genetic therapy such as small inhibitory RNA (siRNA).7 Nanoparticle surfaces, conjugated with a targeting molecule that binds to highly expressed tumor cell receptors, can also facilitate the transport of imaging contrast agents that provide increased sensitivity and specificity, which aid in tumor detection.5

The surfaces of NPs can also be conjugated with drug therapies. 3 Surface conjugation with ligands that specifically bind to the target site can enhance the efficacy of NP drug-delivery systems while significantly reducing toxicity.4 In cancer treatment, tumor targeting can be achieved by conjugating a molecule or biomarker (such as a peptide, protein, or nucleic acid) that is known to bind to tumor cell receptors on the NP surface.5

NPs are generally cleared from circulation by immune system proteins called opsonins, which activate the immune complement system and mark the NPs for destruction by macrophages and other phagocytes.3 Neutral NPs are opsonized to a lesser extent than charged particles, and hydrophobic particles are cleared from circulation faster than hydrophilic particles.3 NPs can therefore be designed to be neutral or conjugated with hydrophilic polymers (such as PEG) to prolong circulation time.3 The bioavailability of liposomal NPs can also be increased by functionalizing them with a PEG coating in order to avoid uptake by the RES.5 Liposomes functionalized in this way are called stealth liposomes.5

NPs are often covered with a PEG coating as a general means of preventing opsonization, reducing RES uptake, enhancing biocompatibility, and/or increasing circulation time.5 SPIO NPs can also be made water-soluble if they are coated with a hydrophilic polymer (such as PEG or dextran), or they can be made amphophilic or hydrophobic if they are coated with aliphatic surfactants or liposomes to produce magnetoliposomes. 5 Lipid coatings can also improve the biocompatibility of other particles.3

NPs can also be designed so that they can be activated to release therapeutic or diagnostic cargo in response to a site-specific or remote trigger.3 Properties that can be used to functionalize NPs for controlled release include pH, temperature, magnetic field, enzymatic activity, or other features such as light or radiofrequency signals.6 NPs constructed with pH-responsive materials can be designed to trigger drug release at a target site upon detecting a change in pH.3 For example, the mildly acidic environment inside inflammatory and tumor tissues (pH 6.8) and cellular vesicles, such as endosomes (pH 5.56.0) and lysosomes (pH 4.55.0), can be exploited to trigger drug release.3

Thermally responsive linkers, consisting of nucleic acids, peptides, proteins, lipids, carbohydrates, or polymers, can also be used to attach one or more agents for controlled release from the NP.3 When the thermally responsive linker is exposed to a specific temperature or temperature range (the trigger temperature), the linker is disrupted and the agent is released.3 For example, DNA molecules with heat-labile hydrogen bonding between complementary strands can act as a heat-sensitive linker.5 An NP can also be designed to include several thermally responsive linkers that are designed to disrupt at different temperatures, enabling drug delivery to occur in a specific order over varied periods of time.3

The release of agents from NPs can also be achieved through the incorporation of bonds that degrade under other specific conditions at the target site.5 For example, tumor-specific processes may be exploited to break a bond and trigger the release of a therapeutic agent.5 Tumor site-specific conditions that could be used to trigger release might include abnormal oxygen levels, unique biomarkers, or exposure to proteolytic enzymes that are overexpressed in tumors.5

The tunability of NP properties is an important and powerful concept.20 NPs have a broad range of tunable biologic, optical, magnetic, electric, and mechanical features that differ dramatically from the same materials in larger forms because of modified quantum mechanics occurring at the nanoscale level.6 By changing the size of an NP, researchers can fine-tune many different properties of nanomaterials.11 For example, they can achieve different colors of fluorescence by changing the size of an NP, allowing a means of color coding or labeling during diagnostic imaging applications.11

Nanomedicines might someday provide answers to longstanding problems in medical research, ranging from poor drug solubility to a lack of target specificity for therapeutic compounds.2 Nanomedicine also has tremendous promise as a noninvasive tool for diagnostic imaging, tumor detection, and drug delivery because of the unique optical, magnetic, and structural properties of NPs that other tools do not possess.1

Nanomedicine presents new opportunities to improve the safety and efficacy of conventional therapeutics.5 Drugs with low bioavailability can now be targeted directly to the site required.3,5 The large surface area and greater reactivity of NPs may allow dose reduction of a drug, which can improve toxicity profiles and patient compliance.2,3 The large surface area of NPs can also increase the dissolution rate, saturation solubility, and intracellular uptake of drugs, improving in vivo performance.2,3 Combining encapsulation, release modalities, and surface modifications to improve therapeutic targeting or bioavailability could improve the efficacy of NP formulations several-fold compared with bulk counterparts.4 Targeted NPs can also transport large doses of therapeutic agents into malignant cells while sparing normal, healthy cells.4,5

One of the most exciting applications of nanomedicine is the use of multifunctional NP complexes for simultaneous non-invasive targeting, imaging, and treatment.1,4,5 Multifunctional NPs for cancer treatment can potentially include a variety of tumor targeting ligands as well as imaging and therapeutic agents that allow noninvasive monitoring and treatment.5 Multifunctional NPs that include fluorescent dyes can also provide in vivo imaging of biologic events during drug administration as well as potential diagnostic labels for the early detection and localization of tumors.7

Recent research efforts are also focused on developing magnetic NPs for the targeted delivery of various therapeutic or diagnostic agents.4 Interest in magnetic NP targeting applications is inspired by the possibility of detecting the particles by MRI and then correlating the results with histologic findings after treatment.3 Polymer/SPIO composites are the most common NPs used for theranostics (diagnostics).3 More than one cancer drug can also be incorporated on a polymer/IO conjugate backbone.3 The drugs can be released at the tumor site, allowing them to act together synergistically, potentially achieving higher efficacy.3 Because SPIO NPs generate heat when exposed to an alternating field, electromagnetic fields can also be applied externally for remote activation of SPIO NPs for thermal ablation therapy.5

Nanotechnologies have already transformed genetic and biological analysis through devices that examine molecular biomarkers.1 Compared with conventional modalities, these tests can be conducted more rapidly, reliably, and cost effectively via in vitro and in vivo diagnostic technologies that, for example, might use nanochips or QDs.1 Nanotechnologies can also produce diagnostic devices that are more sensitive and can detect earlier signs of metabolic imbalances, which can assist in the prevention of diseases like diabetes and obesity.20 The continued application of nanotechnologies to produce better and more cost-effective means of detecting molecular biomarkers will also open the way to the more routine practice of personalized medicine.1

Despite the benefits that nanomedicine has to offer, much research is still required to evaluate the safety and toxicity associated with many NPs.3 Much of nanomedical research has concentrated on drug delivery, with relatively few studies focusing on the pharmacokinetics or toxicity of NPs.7 Investigating NP pharmacokinetics, pharmacodynamics, and potential long-term toxicity in vivo is essential to monitoring the effects of NPs on patient populations.5 Validating every nanotherapeutic agent for safety and efficacy, whether drug, device, biologic, or combination product, presents an enormous challenge for researchers and the FDA, which is currently struggling to formulate testing criteria and accumulate safety data.2,3

Studies are also needed to assess the immunogenicity of NPs.20 Nanotherapeutics and diagnostics may present unexpected toxic effects because of increased reactivity compared with their bulk counterparts.2 The most frequently reported side effect after injection of a nanotherapeutic agent seems to be a hypersensitivity reaction, which may be caused by activation of the immune complement system.6 The main molecular mechanism for in vivo NP toxicity is thought to be the induction of oxidative stress through the formation of free radicals.3 In excess, free radicals can cause damage to lipids, protein, DNA, and other biological components through oxidation. Several authors have reported that intrinsic characteristics of NPs, such as aspect ratio and surface area, can be pro-oxidant and pro-inflammatory.7 However, the formation of free radicals in response to an NP can also have other causes, such as the reaction of phagocytic cells to foreign material, insufficient antioxidants, the presence of transition metals, environmental factors, and other intrinsic chemical or physical properties.3

Research to evaluate the size and surface properties of NPs may also help to identify the critical dimensions at which they tend to significantly accumulate in the body.20 NPs have an increased ability to cross biological barriers and therefore have the potential to accumulate in tissues and cells because of their small size.2 The possible tissue accumulation, storage, and slow clearance of these potentially free radicalproducing particles, as well as the prevalence of numerous phagocytes in the RES, may make organs such as the liver and spleen the main targets of oxidative stress.3,6

This lack of data about potential toxicity issues forces nanomedical research to focus predominantly on polymer NPs, for which safety and efficacy data already exist.3 In fact, several nanomedicines containing polymer NPs are already approved by FDA.3 Unlike other materials that may become toxic in NP form, the lipid NPs are also considered to be biocompatible and tolerable.3 Consequently, biodegradable, soluble, nontoxic NPs, such as polymers, liposomes, and IO particles, are much more desirable to use in nanomedicines than biopersistent components are.5 The use of NPs like carbon nanotubes, QDs, and some metallic nanocarriers that are not biodegradable might be more problematic.1,7 This characteristic need not discourage nanomedical research with these NPs but should reinforce efforts to identify additional biodegradable shapes, materials, and surface treatments.7

Although nanomedicine is still at an early stage of development, several drugs that utilize nanotechnology have been approved and marketed, and many others are being studied.2,3 Nanomedicines potentially offer a means of earlier diagnosis; more effective, safer, and personalized treatments; as well as reduced health care costs.1 Many experts agree that nanomedicine will create a paradigm shift that revolutionizes health care within the next 10 years.2,8 However, for significant progress to be made toward this goal, much more work is needed to establish testing criteria, validate efficacy, and accumulate safety data for various nanotherapeutic agents and materials.2,3

Read the original here:
The Nanomedicine Revolution - PMC - National Center for Biotechnology ...

Number of foreign born residents: 2 (6% naturalized citizens)

63% of Fawn Creek township residents lived in the same house 5 years ago.Out of people who lived in different houses, 62% lived in this county.Out of people who lived in different counties, 50% lived in Kansas.

Median price asked for vacant for-sale houses in 2000: $9,999

Median worth of mobile homes: $29,800

Housing units in Fawn Creek township with a mortgage: 181 (15 second mortgage, 16 home equity loan, 7 both second mortgage and home equity loan)Houses without a mortgage: 159

Year house built

Rooms in owner-occupied houses in Fawn Creek township, Kansas:

Rooms in renter-occupied apartments in Fawn Creek township, Kansas:

Bedrooms in owner-occupied houses and condos in Fawn Creek township:

Bedrooms in renter-occupied apartments in Fawn Creek township:

Cars and other vehicles available in Fawn Creek township in owner-occupied houses/condos:

Cars and other vehicles available in Fawn Creek township in renter-occupied apartments

Owners and renters by unit type in %

Breakdown of mean house values by ages of householders ($)

Most common industries for males (%):

Most common industries for females (%):

Most common occupations for males (%)

Most common occupations for females (%)

Most commonly used house heating fuel:

96.9% of residents of Fawn Creek township speak English at home.1.4% of residents speak Spanish at home (62% speak English very well, 38% speak English not well).0.6% of residents speak other Indo-European language at home (100% speak English very well).1.1% of residents speak Asian or Pacific Island language at home (100% speak English very well).0.1% of residents speak other language at home (100% speak English very well).

Size of family households: 294 2-persons, 167 3-persons, 73 4-persons, 75 5-persons, 12 6-persons, 9 7-or-more-persons,

Size of nonfamily households: 174 1-person, 21 2-persons, 6 3-persons,

391 married couples with children.57 single-parent households (11 men, 46 women).

Educational Attainment (%)

School Enrollment by Level of School (%)

Age and Sex of Sensory-Disabled Residents (Noninstitutionalized)

Age and Sex of Physically-Disabled Residents (Noninstitutionalized)

Age and Sex of Mentally-Disabled Residents (Noninstitutionalized)

Age and Sex of Self-Care Disabled Residents (Noninstitutionalized)

Age and Sex of Go-Outside-Home Disabled Residents (Noninstitutionalized)

Age and Sex of Residents with Employment Disability (Noninstitutionalized)

Year Householders Moved Into Unit in Fawn Creek township:

Read more here:
Fawn Creek township, Montgomery County, Kansas (KS) detailed profile

In this article, we'll explore the population statistics for Fawn Creek, Kansas, including popular demographics data like median age, number of households, household income, gender, employment and unemployment rates, occupations, religion, and more.

We are using the latest American Community Survey (ACS) 5-Year survey data from the US Census Bureau, which is accurate up to 2021.

There is a lot of data that lets us see how many people live in Fawn Creek, Kansas. The most basic data is the total population, which is the total number of people living in Fawn Creek, Kansas. The estimated population of Fawn Creek, Kansas is 1,618 people, with a median age of 46.5.

We can look at the total population in Fawn Creek over the last 5 years to see how much it has changed.

1,618

1,888

+8.19%

1,745

1,853

+10.36%

1,679

We can also look at how the population has changed over the last 5 years by each of the race/ethnicity types as defined by the US Census Bureau.

This data can be very important for a number of reasons, including social and economic research, planning and development, and marketing to a multi-cultural population.

Note that the Native group includes both Native American and Alaskan Native people.

The age and gender of a population is another interesting demographic statistic because it lets us track trends in the population over time. For example, we can see how the population has changed over the last 5 years by median age as a total, and also by male and female.

The median age of Fawn Creek, Kansas gives you an idea of the age distribution, with half of the population being older than the median age and half being younger.

This can then be used to infer and compare against birth rates, parent ages, and more metrics to understand the population. For example, an increasing median age indicates an aging population, which can be a sign of a declining population in terms of birth rates and workforce participation.

The latest median household income of Fawn Creek, Kansas is $58,992.00.

In simple terms, the median income is the middle income of a group of people. Half of the people in the group make more than the median income, and half make less. The median income is a good indicator of the overall income of a group of people, and can be used to compare against other metrics such as the average income, per capita income, and more.

We can also look at the median income by age to see how the median income varies by age, and how it compares to the overall median income for Fawn Creek.

Under 25

$21,667.00

25 to 44

$65,714.00

45 to 64

$77,969.00

65 and over

$37,500.00

Whenever we ask what is the average household income in Fawn Creek, we are actually talking about the mean household income.

This is calculated by adding up all the incomes of all the households in Fawn Creek, and then dividing that number by the total number of households. This is a good way to get a general idea of the average income of a group of people, but it can be skewed by a very high or very low incomes.

The average household income of Fawn Creek, Kansas is currently $71,206.00.

In terms of accurately summarizing income at a geographic level, the median income is a better metric than the average income because it isn't affected by a small number of very high or very low incomes.

If you had an area where the average income was greater than the median, it can mean that there is significant income inequality, with income being concentrated in a small number of wealthy households.

4.51% of households in Fawn Creek are classed as high income households (making $200,000+ per year).

The US Census Bureau divides households into income tiers based on the median income for the area. This is a good way to compare the income of Fawn Creek against other areas.

Less than $24,999

26.78%

$25,000 to $49,999

15.28%

$50,000 to $74,999

19.94%

$75,000 to $99,999

17.03%

$100,000 to $149,999

8.15%

$150,000 to $199,999

8.30%

$200,000 or more

4.51%

The per capita income in Fawn Creek is $32,441.00.

Per capita income is the average income of a person in a given area. It is calculated by dividing the total income of Fawn Creek by the total population of Fawn Creek.

This is different from the average or mean income because it includes and accounts for all people in Fawn Creek, Kansas, including people like children, the elderly, unemployed people, retired people, and more.

We can also look at the education levels in Fawn Creek to see how many people have a high school degree, a bachelor's degree, or a graduate degree.

Educational attainment is a good indicator of the overall education level of a population, and can be used to compare against other metrics such as the average income, per capita income, and more to see how education levels affect income, unemployment rates, and more.

Master's degree or higher

4.89%

Bachelor's degree

18.85%

Some college or associate's degree

9.93%

High school diploma or equivalent

65.61%

Less than high school diploma

0.72%

Employment rates are all based around the total population in Fawn Creek that are over the age of 16.

The total population of Fawn Creek over the age of 16 is 1,375.

Of those people, a total of 60.70% are working or actively looking for work. This is called the labor force participation rate.

The participation rate is a useful market measure because it shows the relative amount of labor resources available to the economy.

The employment to total population rate in Fawn Creek is 56.40%.

We can look at the employment rates by age to see how it compares to the overall employment rate.

Another very interesting employment statistic we can look at is the employment and unemployment rates by race in Fawn Creek. The table below shows the rates for each of the ethnicity groups types defined by the US Census Bureau.

In this section we can look at the most common occupations in Fawn Creek as well as the gender breakdown and earnings of them.

The total population of civilian employees that are 16 years old or older in Fawn Creek is 775, with median earnings of $38,750.00.

Women in Fawn Creek, Kansas earning approximately 66.00% of the men's earnings.

In the table below, we can break down the population and earnings even further by occupation. The list of occupation categories below will show you how many people are employed in each category and the median earnings of each profession.

The table below shows the same occupations from the list above, but we have split them by male and female to see how many male and females work in each occupation, the median earnings, and the male to female ratio of earnings.

That last metric is important because it can be used to look at the gender pay gap between men and women.

A household defined bu the US Census Bureau is a group of people who occupy a housing unit. A housing unit is a house, apartment, mobile home, group of rooms, or single room occupied as separate living quarters.

There are currently 687 households in Fawn Creek, with an average household size of 2.36 people.

A family is defined as a group of two or more people related by birth, marriage, or adoption who live together in the same household.

There are 490 families in Fawn Creek with an average family size of 2.68 people.

The four categories of household by marital status are:

The table below shows the total number of households and families, with the average sizes of each.

Of the 490 families in Fawn Creek, 15.30% are considered to be below the poverty threshold.

The table below shows the latest poverty thresholds in Fawn Creek:

There are 764 housing units in Fawn Creek, Kansas.

The table below shows the split between occupied and vacant units:

4.84% of the total 764 housing units in Fawn Creek are rental units. This is approximately 37 properties.

For owner-occupied housing units, a total of 615 are occupied by the owner - or 80.50% of the total.

The median rent for a property in Fawn Creek is $1,079.00.

In the chart below, we can look at the number of rental properties in Fawn Creek that fall into a particular rent range. These can then be used to compare with other areas, or to see how they have changed over time.

No rent paid

35

Less than $500

0

$500 to $999

10

$1,000 to $1,499

27

$1,500 to $1,999

Excerpt from:
Fawn Creek, Montgomery County, Kansas Population and Demographics

An Introduction to Nanomedicine  AZoNano

Read more:
An Introduction to Nanomedicine - AZoNano

Nanomedicine Market is expected to show growth from 2024 to 2030, reported by Maximize Market Research  openPR

See the article here:
Nanomedicine Market is expected to show growth from 2024 to 2030, reported by Maximize Market Research - openPR

Oro Rx Healthcare LLP Unveils Oroceuticals: The Next-Gen Nutrition Delivery Tech  Hindustan Times

Original post:
Oro Rx Healthcare LLP Unveils Oroceuticals: The Next-Gen Nutrition Delivery Tech - Hindustan Times

Leapfrogging as pharma leader of the worldNational Policy on Research and Development and Innovation in Pharma-MedTech Sector in India  The Sangai Express

Here is the original post:
Leapfrogging as pharma leader of the worldNational Policy on Research and Development and Innovation in Pharma-MedTech Sector in India - The Sangai...

What will Indian healthcare look like in 2047? Robotics, AI, biotech will shape the future  The Economic Times

Original post:
What will Indian healthcare look like in 2047? Robotics, AI, biotech will shape the future - The Economic Times

AI-generated image using Midjourney depicting scientists inventing new medicines

In 1998 I was exposed to the term disruptive innovation for the first time. I read a wonderful book, The Innovators Dilemma by Clayton Christensen, where I learned the difference between incremental innovation and disruptive innovation. He analyzed the hard drive industry and showed that while many companies were trying to increase the capacity of the drives, other companies changed the form factor and made the drives smaller. This resulted in disruptive progress in the industry. We also recently witnessed dramatic advances in artificial intelligence (AI), where in 2013/2014 AI systems started outperforming humans in image recognition. This was made possible by taking several existing technologies, deep neural networks (DNNs) and GPU computing, and training DNN on really big data sets. In fact, disruptive innovation often results from the combination of already existing technologies to make them work to address a massive unmet need.

Over past decades, the field of nanomedicine, mostly characterized by the targeted delivery of drugs for numerous types of diseases, has gained a special attention in oncology research. While some anti-cancer drugs work well when administered to the right patient and in the right dose, no drug is perfect, and no dose fits all. One of the most frequently used classes of anti-cancer drugs is platinum-based compounds, such as carboplatin, oxaliplatin, and cisplatin (one of the most effective anti-cancer drugs for the treatment of solid malignancies). Chemotherapeutic agents are necessarily toxic, as from a therapeutic stance, we need to kill the rapidly dividing cancer cells. However, as these drugs are nonselective (targeting both healthy and malignant tissues), patients often suffer the unfortunate combination of substantial side effects and low efficacy at the target site when these compounds are administered systemically via traditional routes (orally or intravenously).

Enhancing the accumulation of these drugs locally at the tumor site may significantly reduce the systemic toxicities and adverse side effects, while simultaneously improving treatment efficacy substantially. The major limitation is that these drugs do not penetrate very well, and so enhancing penetration has become a necessary goal in the optimization of delivering these agents. One technology that can help with this task is encapsulating the chemotherapeutic agents in nanoparticles (NPs). During the last decade, a wide range of nano-based drug delivery systems has been explored as alternative cisplatin delivery methods that may promote its accumulation and retention in cancer cells. While some of these NP formulations have demonstrated promising preclinical results and a few have entered clinical trials, none have been approved for the treatment of human cancers. Targeted accumulation of the drug can be further optimized through topical delivery of NPs in the form of gels and film composites, which may also increase the local and precise administration of chemotherapeutic drugs to accessible tumors (such as cancers arising in the oral cavity). Therefore, disruptive innovation has originated from merging these approaches and generating topical NP-based drug delivery platforms that primarily intend to ameliorate the adverse effects of systemically administered treatment and maximize the total dose and retention of the carried therapeutic agent at the local site, improving treatment efficacy.

Manijeh Goldberg, PhD, MBA, CEO of Privo Technologies

A multidisciplinary group led by Dr. Manijeh Goldberg, founder and CEO of Privo Technologies, together with Dr. Nishant Agrawal and Dr. Evgeny Izumchenko, Chief of Head and Neck Surgery and Professor of Hematology and Oncology at the University of Chicago, respectively, recently published the results of Privos preclinical and clinical studies using PRV111 treatment. This treatment is a topical mucoadhesive cisplatin delivery system that has the potential to revolutionize the field.

A screen capture of the header of the Nature Communications paper titled "A nanoengineered topical ... [+] transmucosal cisplatin delivery system induces anti-tumor response in animal models and patients with oral cancer" https://doi.org/10.1038/s41467-022-31859-3

In the recent Nature Communications paper titled A nanoengineered topical transmucosal cisplatin delivery system induces anti-tumor response in animal models and patients with oral cancer, the scientists describe a nanotechnology-based patch system for non-invasive, local delivery of cisplatin-loaded chitosan particles that penetrate tumor tissue and lymphatic channels while avoiding systemic circulation and toxicity. The system was used in both animal models (mice and hamsters) and patients with oral cancer and demonstrated promising, potentially disruptive, results.

Professor Nishant Agrawal, MD, Director, Head and Neck Surgical Oncology Chief, Section of ... [+] Otolaryngology-Head and Neck Surgery, University of Chicago

The hamster cheek model is a well-characterized system for studying oral cancer because of the similarities between the tissue in the pouch and the tissue in the human mouth. In the clinical trial, patients were treated with PRV111 as long as a week before undergoing surgery (surgery is standard for all patients with oral cancer). 87% of patients responded to treatment and showed decreased tumor volume, with an average decrease of 70% of tumor volume across all patients. As further confirmation of PRV111s efficacy, examination of the tumor tissue after surgery demonstrated that treatment also stimulated the patients innate immune system. Thus, the results from PRV111 use in humans suggest that PRV111 has shown a one-two punch therapeutic effect, simultaneously killing tumor cells and recruiting immune cells to attack the tumor site.

Briefly, in the PRV111 platform, chitosan (a non-toxic, biocompatible, and biodegradable polysaccharide derived from natural chitin), is used as a polymer for both the NPs and the porous matrix. As such, matrix-based water-soluble chitosan acts as a bioadhesive since the positively-charged chitosan can bind to negatively-charged mucoproteins, allowing the electrostatic interaction with mucin proteins in the oral cavity. Each cisplatin-loaded chitosan NPs containing patch covers a tumor region of 4 cm2, and incorporates a permeation enhancer that allows optimal penetration and absorption of the NPs released from the patch. When exposed to moisture, the NPs swell, allowing them to diffuse across the porous matrix and into the tumor tissue. However, these particles are too large to penetrate into the vasculature, and therefore prevent systemic cisplatin exposure.

Professor Evgeny Izumchenko, PhD

Since I made a tiny and insignificant contribution to the paper, and I am familiar with the leading authors. I got a chance to ask them a few questions about this possibly groundbreaking work.

Alex: I consider cisplatin to be one of the ancient uber-toxic cancer drugs that are responsible for the many misconceptions about modern cancer treatments. Why did you choose cisplatin for this study?

Cisplatin is one of the most potent anti-cancer agents. It has been studied and used in the field of oncology for decades. However, its dose-limiting systemic toxicities such as nephrotoxicity, ototoxicity and neurotoxicity can be severe and many times irreversible. In its early days, Privo discussed the best choice for its active ingredient with its advisor at the time, Dr. Jos Baselga at Bostons Mass General Hospital (MGH). Dr. Baselga, a renowned cancer researcher and the chief of hematology/oncology at MGH, recommended using cisplatin. He noted that cisplatin is a beast of a cancer drug and if tamed, it can be extremely effective in destroying cancer cells. Privo optimized the use of cisplatin to reduce its nasty systemic side effects while significantly improving its efficacy by its ability to directly deliver high concentrations of cisplatin to the tumor. This is like an atomic bomb applied specifically to the tumor, sparing the patients healthy tissues.

Alex: Nanomedicine is a frequently overused word, and it defines a very broad field. How do your group and your consortium of collaborators fit into this field?

We use both nano- and micro-particles in our matrix as part of our two-stage release platform technology. We design the particles with specific properties such as surface chemistry and size. The nano- and micro-particles can be programmed to control the release of the active ingredient based on the treatment requirements. In addition, the particle-containing polymeric matrix further protects the particles, allowing for longer lasting drugs following administration. For example, cisplatin is a very volatile drug which rapidly binds to proteins in the body, causing its deactivation before it can even reach the tumor site and have the chance to destroy cancer cells. Privos PRV111 is designed to protect and effectively insulate the drug for much longer, serving to decrease side effects and increase cellular uptake of the drug. The surface chemistry of the particles can also be optimized to increase cellular uptake further.

Alex: Can you tell me the story behind this paper - how did it come together?

Privo has been collaborating with Dr. Nishant Agrawal from Chicago Medicine since its early development days. I was introduced to Dr. Agrawal via a mutual friend, who was an oncologist that had lost a friend to oral cancer. He saw the potential of our research helping patients suffering from head and neck cancers. Dr. Agrawal is the chief of head and neck surgical oncology team at UChicago Medicine and has been a great mentor to our Privo team in addition to being a champion of our platform technology. Once Privo had successful preclinical data followed by phase 1 / 2 clinical study, the team agreed to publish the results. During the several years of research, Dr. Agrawal has made several introductions to other key opinion leaders such as Dr. Evgeny Izumchenko, an expert head and neck researcher at the University of Chicago who has been instrumental in compiling and publishing the data.

Alex: How much impact will this study have on patient lives once the technology reaches the market?

I think Privos technology has the potential to disrupt the treatment paradigm for several cancers starting with mucosal cancers such as oral, lung, cervical, and even brain tumors.

In todays world, social media has provided an unbiased, uncomfortable, and often raw insight into what a cancer patients journey is like. Over the past several years, we have followed a few oral cancer patients on their journey from initial diagnosis, treatment, surgery, physical therapy in addition to their mental health journey at each step of the road. Oral cancer has one of the highest suicide rates among cancers, and is second only to pancreatic cancer in terms of quality of life. Considering the accessibility of oral cancer, we aim to provide patients with a better alternative that offers them a better quality of life. Our data collected to date has shown that PRV111 has significantly reduced tumor volume for patients with T1/T2 stage tumors. In our Phase 3 design, we aim to target an early form of oral cancer, carcinoma in situ, where our goal is to eliminate the need for surgery indefinitely.

Alex: Are you planning to commercialize the technology and what are your plans to take it to market?

We are planning to commercialize the technology, especially after the successful first-in-human trial, which showed that PRV111 treatment performed better than expected, leading to early completion of the study. On average, PRV111 treatment decreased tumor volume by about 70% in just one week. Privo has successfully received support and collaboration from the FDA-OOPD, the NIH-NCI, the NIH-NIDCR, and the NSF. Their guidance and support is helping us be well on our way toward market approval.

In principle, this novel mucoadhesive system can be engineered to deliver virtually any chemotherapy and non-chemotherapy agent with a particular drug release profile, making it customizable for specific clinical applications. The unique properties of this carefully designed nanomedicine provide a promising framework and holds potential for the improved treatment of not only oral accessible cancers but also other solid malignancies.

Professor Alexander T Pearson, MD, PhD, Professor Evgeny Izumchenko, PhD, Alex Zhavoronkov, PhD at ... [+] the University of Chicago

Link:
Going Beyond Target Or Mechanism Of Disease: Disruptive Innovation In Drug Delivery Systems - Forbes

The Global Nanomedicine Market 2022 research report presents an in-depth analysis of the Nanomedicine Market size, growth, share, segments, manufacturers, and forecast, competition landscape and growth opportunity. The researchs goal is to provide market data and strategic insights to help decision-makers to make educated investment decisions while also identifying potential gaps and development possibilities.We also analysed the impact of COVID-19 (Corona Virus) on the product industry chain based on the upstream and downstream markets, on various regions and major countries and on the future development of the industry are pointed out.

The market size was determined by estimating the market through a top-down and bottom-up approach, which was further validated with industry interviews. Considering the nature of the market we derived it by segment aggregation, the contribution of the materials and vendor share.

Click Here to Download and Understand Latest Key Trends On Nanomedicine Market

https://skyquestt.com/sample-request/nanomedicine-market

Companies involved in theNanomedicine Market research report are:

What exactly is included in the Report?

Industry Trends and Developments:In this section, the authors of the research discuss the significant trends and developments that are occurring in the Nanomedicine Market place, as well as their expected impact on the overall growth.

Analysis of the industrys size and forecast:The industry analysts have provided information on the size of the industry from both a value and volume standpoint, including historical, present and projected figures.

Future Prospects:In this portion of the study, Nanomedicine Market participants are presented with information about the prospects that the Nanomedicine Market industry is likely to supply them with.

The Competitive Landscape:This section of the study sheds light on the competitive landscape of the Nanomedicine Market by examining the important strategies implemented by vendors to strengthen their position in the Nanomedicine Market.

Study on Industry Segmentation:This section of the study contains a detailed overview of the important Nanomedicine Market segments, which include product type, application, and vertical, among others.

In-Depth Regional Analysis:Vendors are provided with in-depth information about high-growth regions and their particular countries, allowing them to place their money in more profitable areas.

Speak with our analyst for more information:

https://skyquestt.com/speak-with-analyst/nanomedicine-market

Key Offerings:

About Us:

SkyQuest Technologyis leading growth consulting firm providing market intelligence, commercialization and technology services. It has 450+ happy clients globally.

Address:

1 Apache Way, Westford, Massachusetts 01886

Phone:

USA (+1) 617-230-0741

Email:[emailprotected]

Find Insightful Blogs/Case Studies on Our Website:

Market Research Case Studies

Read the original here:
Nanomedicine Market Size, Share, Types, Products, Trends, Growth, Applications and Forecast 2022 to 2028 - Digital Journal

Noninvasive ventilation is possible in infants at limits of viability. But unlike in slightly older preterm infants, noninvasive ventilation did not show an advantage in infants of 22 weeks-0 days to 23 weeks-6 days gestational age.

Vivek Shukla, right, and Brian Sims, left, help hold Guinness World Records Certificate for Most Premature Baby to Survive, awarded in honor of mother Michelle Butler and child Curtis Means, born at 21 weeks gestation (center). Adults are masked for COVID precautions in 2021. Photography: Andrea MabryExtremely premature infants still face daunting risks of sickness or death, even though advances in neonatal-perinatal care have improved infant survival at progressively lower gestational ages. Bronchopulmonary dysplasia a serious condition of undeveloped lungs is a leading morbidity in these tiny infants.

Studies have shown that noninvasive respiratory support at birth rather than immediate intubation and delivery of lung surfactant improves short-term respiratory outcomes in premature infants born at gestational age 24 weeks-0 days to 27 weeks-6 days.

So, clinicians at the University of Alabama at Birmingham led by Charitharth Vivek Lal, M.D., and Vivek Shukla, M.D., asked whether the same was true for the tiny newborns at the limits of viability, whom they categorize as nano-preterm infants those born at gestational age 22 weeks-0 days to 23 weeks-6 days. These nano-preterms compose a highly specialized niche subgroup that is considerably more immature and has much higher risks of mortality and morbidity than the 24- through 27-week gestational age preterms, Lal says.

A full-term pregnancy is 39 to 40 weeks.

In one of the largest studies of this population, UAB researchers did a retrospective analysis of 230 consecutively born, eligible nano-preterm infants born from January 2014 through June 2021 at the UAB level IV neonatal intensive care unit. Eighty-eight infants in the noninvasive group were those whose first intubation attempt was more than 10 minutes after birth, and 142 infants in the invasive respiratory support at birth were those intubated within 10 minutes after birth. Unlike in several previous studies of slightly older pre-term infants, Lal and colleagues found no benefits for the noninvasive respiratory support of those nano-preterm infants, as measured by the composite outcome of bronchopulmonary dysplasia or death by 36 weeks postmenstrual age.

Vivek Lal, M.D.Some 94.3 percent of the noninvasive group and 90.9 percent of the invasive group had bronchopulmonary dysplasia or death by 36 weeks, which was not a significant difference. The clinicians did see that severe intraventricular hemorrhage or death by 36 weeks was lower in the invasive respiratory support group, a trend that will require a larger number of infants to confirm.

This cohort studys findings suggest that noninvasive respiratory support in the first 10 minutes after birth is feasible but may not be associated with a decrease in the risk of bronchopulmonary dysplasia or death compared with intubation and early surfactant delivery in nano-preterm infants, said Lal, an associate professor in the UAB Department of Pediatrics, Division of Neonatology. Shukla is an assistant professor in the Division of Neonatology.

The average weight of the noninvasive nano-preterm infants was 1 pound 4.4 ounces, and the average weight of the invasive preterm infants was 1 pound 2.4 ounces.

The study, Hospital and neurodevelopmental outcomes in nano-preterm infants receiving invasive vs noninvasive ventilation at birth, is published in the journal JAMA Network Open.

Co-authors with Lal and Shukla are Grant Imbrock, Colm P. Travers, Namasivayam Ambalavanan and Waldemar A. Carlo, UAB Department of Pediatrics, Division of Neonatology; and J. Paige Souder, Muhan Hu and A.K.M. Fazlur Rahman, Department of Biostatistics, UAB School of Public Health.

Support came from National Institutes of Health grant HL141652, UAB and Childrens of Alabama.

Pediatrics is a department in the Marnix E. Heersink School of Medicine at UAB.

Read the rest here:
Nano-preterm infants may not benefit from noninvasive versus invasive ventilation at birth - University of Alabama at Birmingham

Spanish-American clinical research executive Juan de Borbn resides in the United States. He has vast experience running nearly 2000 clinical trials in various therapeutic fields. These include cancer, nephrology, hepatology, infectious illness (Covid-19, Ebola, Marburg, Influenza, HIV, Hepatitis), and neurology. Juan de Borbn has been inspiring and motivating the clinical drug development sector for more than 20 years by utilizing his extensive industry knowledge.

Alfonso XIII of Spains senior great-grandson Juan de Borbn is his matrilineal direct descendant. King Alfonso XIII of Spain and his wife, Princess Victoria Eugenie of Battenberg, had a son, Alfonso, the oldest of five siblings. Alfonso, Prince of Asturias, who lived from 10 May 1907 to 6 September 1938, was the presumptive heir to the Spanish crown and grandfather to Juan. At the time, Alfonsos renunciation and untimely death as the heir to Spains monarchy sparked debate. King Felipe VI of Spain, his cousin, now sits the Spanish throne.

At the age of two months, Juan de Borbn immigrated to the US and spent his formative years in Los Angeles. Growing up, he practiced martial arts, surfed, skateboarded, and shared a deep passion for baseball with his father. His parents wished for him to have a wider variety of experiences and a deeper appreciation of his roots. Today, he is a top-ranking CEO honored for his accomplishments and model leadership by the business, his employers, and coworkers; Juan now holds the positions of Principal and President of Global Strategy at Global Earth USA, Executive Chairman of Borbon dAnjou Holdings, and Principal of the Borbon Family Office.

He is a compassionate leader who upholds the principles of integrity, honesty, and creativity, collaborating directly with Nano Cures Pharma in 2021 to provide Covid-19 vaccinations to underserved countriesworking now with Thailand and the Central African Republic to obtain Emergency Use Authorization for the vaccination in those nations.

Juan de Borbn established the first American Heart Training Center in a Clinical pharmacology facility in 2017, guaranteeing the best level of staff training in acute care for research participants. He combined WCCT with Medelis, an institution that conducts oncology clinical research, in 2016. The deal focused on the complex and quickly expanding oncology drug development industry in the United States, Europe, and Asia. This requires a unique answer with knowledge, insight, and a focus on the future.

With a focus on oncology, ophthalmology, gastroenterology, gastrointestinal, renal, hepatic, and virology, Juan de Borbn created a multisite management service offering CRO Services for WCCT in 2014. This service provided data processing, statistics, medical monitoring, drug safety, tracking, site selection, and site management. He established the early clinical research facilities for cosmetology and ophthalmology in 2013 and combined OC Clinical Trials & Consulting with WCCT Global.

Juan believes that the era of doing regular activities in healthcare is finished. Despite the tireless efforts of well-meaning, well-trained professionals, every health care system in the world is battling escalating prices and unequal quality. Health care leaders and policymakers have attempted to combat fraud, reduce errors, enforcing practice guidelines, improve patient consumers, and deploy electronic medical records. Still, none of them have had much of an impact. It is time for a whole different approach.

He is focused on shifting from a supply-driven, physician-centered healthcare system to one that is patient-centered, patient-centered, and organized around patient needs. A system where services for specific medical diseases are focused in health-delivery organizations and in the appropriate places to deliver high-value care must be put in place to replace the fragmented system of today, in which every local provider offers a broad range of services. The volume and financial success of the services providedphysician visits, hospital stays, operations, and testsmust be shifted to the success of the patient outcomes.

Juan aims to launch the worlds first medical metropolis to promote lifespan and good health while utilizing information and communications technology for the exchange of reliable data for the assessment, care, and prevention of illness and injuries, research, and evaluation, as well as for the continuing education of health care professionals, all to improve the health of people and their communities. Additionally, it is intended to assist the patient in maintaining their performance level throughout their entire lifespan. The main risk factor for most diseases is advancing age, particularly of cellular structures, and life expectancy in the population is still rising.

Juan emphasizes that the cutting-edge longevity center offers tailored preventative medicine by implementing methods to promote healthy aging, delay diseases primarily related to aging, and lengthen a persons active time of life. Providers who continue to use the outdated methods of today will go extinct. Reputations that are built on perception rather than actual results will deteriorate. In the face of increased openness and declining reimbursement levels, maintaining present cost structures and prices will be impossible. The only reputation that should matter in health care is assisting people in leading the healthiest and longest-lasting lives possible.

Have you read?The Worlds Largest Economies, 2022.International Financial Centers Ranking, 2022.These are the countries with the Highest Average Salaries, 2022.CEO Spotlight: For Plaintree Systems CEO David Watson, the Future is Taking Its Cues From the Past.How to Build a Winning Sales Team That Gets your Business Soaring by Jakob Wissel.When Culture Matters by Bill Yeargin.

More here:
Juan De Borbon - Introducing Cutting-Edge Techniques To The Healthcare Industry - CEOWORLD magazine