Nanomedicine

Precision Medicine is still an evolving research and policy space some 18 months after the initial White House policy announcement.
• There is little evidence of a mainstream public discourse about the PMI yet.
• These audiences get their information directly from the media statements, rather than journalists
• Concerns about the use of genetic screening to target and segment populations for treatment have been discussed by academics such as Charmaine Royal, Jonathan Kahn and Dorothy Roberts. The PMI brings such concerns to the attention of policy-makers.
• There is little evidence of Australian involvement in online discussions about the PMI.

Introduction: Carbon nanotubes (CNTs) have been widely employed as biomolecule carriers, but there is a need for further functionalization to broaden their therapeutic application in aqueous environments. A few reports have unraveled biomolecule-CNT interactions as a measure of response of the nanocarrier to drug-encapsulation dynamics. Methods: Herein, the dynamics of encapsulation of the antimicrobial peptide HA-FD-13 (accession code 2L24) into CNTs and hydroxylated CNTs (HCNTs) is discussed. Results: The van der Waals (vdW) interaction energy of CNT-peptide and HCNT-peptide complexes decreased, reaching −110.6 and −176.8 kcal.Mol −1 , respectively, once encapsulation of the peptide inside the CNTs had been completed within 15 ns. The free energy of the two systems decreased to −43.91 and −69.2 kcal.Mol −1 in the same order. Discussion: The peptide was encased in the HCNTs comparatively more rapidly, due to the presence of both electrostatic and vdW interactions between the peptide and HCNTs. However, the peptide remained encapsulated throughout the vdW interaction in both systems. The negative values of the free energy of the two systems showed that the encapsulation process had occurred spontaneously. Of note, the lower free energy in the HCNT system suggested more stable peptide encapsulation.

Objective: Morphine can cause harmful effects in the ovaries. But its effect on reproductive (hypothalamus-pituitary-gonad) axis is not clearly known. Today, silver nanoparticles are widely used in healthcare products because of antimicrobial properties. These particles can pass the blood-brain barrier and change in the nitric oxide level. We studied the effect of pre-injection of Ag-NPs prior to morphine (intra-VMH) in order to investigate the protective effect on the rat's polycystic ovary induced of morphine. The effects were also compared with those observed in the morphine addicted animal. Materials and Methods: The rats (200-250 g) were housed under standard conditions and fed ad libitum. They were randomly divided into addicted to morphine (10-100 mg/kg, i.p., 7 days, twice daily) or receiving the drug (0.001 to 0.4 μg/rat, once, intra-VMH) (AP:-1.92), a week after stereotaxic surgery. Ag-NPs (0.01, 0.001 and 0.0001 μg/rat) were administered for once (intra-VMH) alone or prior to the morphine effective dose (0.4 μg/rat). Control group was given only saline. At the end, the animals' ovaries and/or brain both histopathologically and by NADPH-diaphorase were examined. Results: All rats' ovaries treated morphine showed polycystic features compared with the saline group (p<0.05). The activation of the NO system in the ovaries was also evidenced by NADPH-diaphorase. However, with pre-injection of the Ag-NPs, (intra-VMH) to morphine, the number of cysts was reduced and the VMH neurons were protected. Conclusion: The Ag-NPs may inhibit the morphine-induced PCO by decreasing the level of NO in the ovary through protection of hypothalamic neurons.

Quantum dots (QDs) are fluorescent semiconductor nanocrystals that have the potential for major advancements in the field of nanomedicine through their unique photophysical properties. They can potentially be used as fluorescent probes for various biomedical imaging applications, including cancer localization, detection of micrometastasis, image guided surgery, and targeted drug delivery. Their main limitation is toxicity, which requires a biologically compatible surface coating to shield the toxic core from the surrounding environment. However, this leads to an increase in QD size that may lead to problems of excretion and systemic sequestration. We describe a one pot synthesis, characterization, and in vitro cytotoxicity of a novel polyhedral oligomeric silsesquioxane (POSS)-coated CdTe-cored QD using mercaptosuccinic acid (MSA) and D-cysteine as stabilizing agents. Characterization was performed using transmission electron microscopy Fourier transform infrared spectroscopy, and photoluminescence studies. POSS-coated QDs demonstrated high colloidal stability and enhanced photostability on high degrees of ultraviolet (UV) excitation compared to QDs coated with MSA and D-cysteine alone (P value , 0.05). In vitro toxicity studies showed that both POSS and MSA-QDs were significantly less toxic than ionized salts of Cd +2 and Te −2 . Confocal microscopy confirmed high brightness of POSS-QDs in cells at both 1 and 24 hours, indicating that these QDs are rapidly taken up by cells and remain photostable in a biological environment. We therefore conclude that a POSS coating confers biological compatibility, photostability, and colloidal stability while retaining the small size and unique photophysical properties of the QDs. The amphiphilic nature of the coating allows solubility in aqueous solutions and rapid transfer across cell membranes, enabling the use of lower concentrations of the QDs for an overall reduced toxicity particularly for prolonged live cell and in vivo imaging applications.

Over the last decades Nanotechnology has promised to advance science and technology in many areas. Within medicine, Nanomedicine promises to deliver new methods for diagnosis, prognosis and therapy. As the amount of available information is rapidly growing, new Biomedical Informatics approaches have to be developed to satisfy the increasing demand on data and knowledge management. In 2007, a new sub-discipline, already named &quot;Nanoinformatics&quot;, was created with support from the US National Science Foundation. In Europe, a project named ACTION-Grid was launched in 2008 with support from the European Commission to analyze the challenges and agenda for developing Nanoinformatics as a discipline related to Nanotechnology, Biomedicine and Informatics. For MIE 2009, members of this consortium proposed a workshop to discuss the scientific and strategic issues associated with this topic. Nanoinformatics aims to create a bridge between Nanomedicine and Information Technology applyin...

During the last decade, the application of nanotechnologies for anticancer drug delivery has been extensively explored, hoping to improve the efficacy and to reduce side effects of chemotherapy. The present review is dedicated to a certain kind of anticancer drug nanovectors developed to target tumors with the help of an external magnetic field. More particularly, this work treats anticancer drug nanoformulations based on superparamagnetic iron oxide nanoparticles coated with biocompatible polymers. The major purpose is to focus on the specific requirements and technological difficulties related to controlled delivery of antitumoral agents. We attempt to state the problem and its possible perspectives by considering the three major constituents of the magnetic therapeutic vectors: iron oxide nanoparticles, polymeric coating and anticancer drug.

Background: Theranostic nanomaterials composed of fluorescent and photothermal agents can both image and provide a method of disease treatment in clinical oncology. For in vivo use, the near-infrared (NIR) window has been the focus of the majority of studies, because of greater light penetration due to lower absorption and scatter of biological components. Therefore, having both fluorescent and photothermal agents with optical properties in the NIR provides the best chance of improved theranostic capabilities utilizing nanotechnology. Methods: We developed nonplasmonic multi-dye theranostic silica nanoparticles (MDT-NPs), combining NIR fluorescence visualization and photothermal therapy within a single nanoconstruct comprised of molecular components. A modified NIR fluorescent heptamethine cyanine dye was covalently incorporated into a mesoporous silica matrix and a hydrophobic metallonaphthalocyanine dye with large molar absorptivity was loaded into the pores of these fluorescent particles. The imaging and therapeutic capabilities of these nanoparticles were demonstrated in vivo using a direct tumor injection model. Results: The fluorescent nanoparticles are bright probes (300-fold enhancement in quantum yield versus free dye) that have a large Stokes shift (.110 nm). Incorporation of the naphthalocyanine dye and exposure to NIR laser excitation results in a temperature increase of the surrounding environment of the MDT-NPs. Tumors injected with these NPs are easily visible with NIR imaging and produce significantly elevated levels of tumor necrosis (95%) upon photothermal ablation compared with controls, as evaluated by bioluminescence and histological analysis. Conclusion: MDT-NPs are novel, multifunctional nanomaterials that have optical properties dependent upon the unique incorporation of NIR fluorescent and NIR photothermal dyes within a mesoporous silica platform.

Superparamagnetic iron oxide nanoparticles are candidate contrast agents for magnetic resonance imaging and targeted drug delivery. Biodistribution and toxicity assessment are critical for the development of nanoparticle-based drugs, because of nanoparticle-enhanced biological reactivity. Here, we investigated the uptake, in vivo biodistribution, and in vitro and in vivo potential toxicity of manganese ferrite (MnFe 2 O 4) nanoparticles, synthesized by an original high-yield, low-cost mechanochemical process. Cultures of murine Balb/3T3 fibroblasts were exposed for 24, 48, or 72 hours to increasing ferrofluid concentrations. Nanoparticle cellular uptake was assessed by flow-cytometry scatter-light measurements and microscopy imaging after Prussian blue staining; cytotoxicity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony-forming assays. After a single intravenous injection, in vivo nanoparticle biodistribution and clearance were evaluated in mice by Mn spectrophotometric determination and Prussian blue staining in the liver, kidneys, spleen, and brain at different posttreatment times up to 21 days. The same organs were analyzed for any possible histopathological change. The in vitro study demonstrated dose-dependent nanoparticle uptake and statistically significant cytotoxic effects from a concentration of 50 µg/mL for the MTT assay and 20 µg/mL for the colony-forming assay. Significant increases in Mn concentrations were detected in all analyzed organs, peaking at 6 hours after injection and then gradually declining. Clearance appeared complete at 7 days in the kidneys, spleen, and brain, whereas in the liver Mn levels remained statistically higher than in vehicle-treated mice up to 3 weeks postinjection. No evidence of irreversible histopathological damage to any of the tested organs was observed. A comparison of the lowest in vitro toxic concentration with the intravenously injected dose and the administered dose of other ferrofluid drugs currently in clinical practice suggests that there might be sufficient safety margins for further development of our formulation.

The goal of the current study was to explore the potential benefits of Acitretin (Act) nanovesicular gel as a prospective antipsoriatic topical delivery system counteracting the drug challenges in terms of its extremely low aqueous solubility, instability, skin irritation, and serious systemic adverse effects. Act-loaded niosomes were successfully developed, entirely characterized, and optimized. Further evaluation of the optimized formula was conducted regarding its stability and ex vivo cytotoxicity on different cell lines. The optimized niosomal vesicles were then incorporated in gel base matrix and investigated by sequential ex vivo (skin permeation and deposition) and in vivo (skin irritation and antipsoriatic activity using mouse tail model) experiments. The optimized Act-loaded niosomes (span 60:cholesterol molar ratio 1:1) were spherical in shape and exhibited the highest entrapment efficiency (90.32±3.80%) with appropriate nanosize and zeta potential of 369.73±45.45 nm and ...

The deadliest types of blood-related, and solid tumors due to chemoresistance, radioresistance and immunoresistance include GBM, CRC, Breast Ca, Prostate Ca, Lung Ca, Pancreatic Ca, AML, ALL, MDS, MPN, Leukemia, Lymphoma, Multiple Myeloma,  etc.
Oncogenic, metastatic and resistant to treatment molecular pathways to be circumvented consist of epigenomic-alterations, quiescent-CSC evading immune-surveillance and response, EMT, activation of genomic tumor proliferative signaling-pathways, activation of MDR and detoxification-proteins, reprogramming involving energy of tumor-metabolism and metabolic-shift, lack of homeostasis involving  mitochondrial-ions, minactivation and detoxification of drug-molecules, deficient-repair after DNA-damage, hostile tumor-microenvironment involving autophagy, inflammatory-factors or hypoxia, cellular-ability of self renewal, resistance to induction of apoptosis especially after DNA-damage, activation of invasive, migratory and metastatic-factors involving angiogenesis and lymphoangiogenesis, etc.   
Thus, oncology requires radical improvements involving screening, diagnosis, prevention, monitoring, prognosis and mainly treatment, which has to be tailored to the clinical phenotype of each cancer-patient which has to be linked to the disease related genotype, and mainly epigenotype for the implementation of precision and personalized medicine approaches.
Epigenomic alterations which may be detected by pharmacoepigenomics may activate the pathogenesis of tumors  by interfering with the expression of disease related protein coding genes. This phenomenon may also affect the clinical response to conventional therapeutic approaches by creating drug resistance. Also, epigenomic testing may circumvent the diagnostic odyssey in oncology, and since epigenomic alterations are reversible we can prevent the development of cancer by influencing the associated expression of the disease related deleterious variants in protein coding genes. In case cancer has already been developed, we can tailor precision and personalized medicine approaches by targeting the disease related deleterious epigenomic alterations, and variants in protein coding genes by combining results from pharmacogenomics and pharmacoepigenomics for eradicating the disease, suppress its symptoms or improve the chemosensitivity and therapeutic index of the administered therapeutic agents. In this process, we may also utilize personalized data generated by cancer-multiomics including immunogenomics, nutrigenomics, metabolomics, lipidomics, immunogenomics, interactomics, glycomics, transcriptomics, proteomics, epiptoteomics, epitranscriptomics, genomics, DNA and RNA epigenomics, etc. This way we may target chemo, radio, and immunoresistant mechanisms leading to the induction of apoptosis or PCD type-I, and subsequent bystander killing effect. Furthermore, Next Generation Sequencing or NGS may lead to the discovery of novel cancer  related genes and variants, which may be used as novel biomarkers for screening, diagnosis, prevention, monitoring, prognosis and mainly for anticancer targeted therapy.
Emphasis must be given on the reversible epigenetic alterations which may interact with each other creating the new discipline of epi-interactomics, which includes interactions among post-translational alterations of histone-tails including phosphorylation, methylation, ubiquitination, deacetylation and mainly acetylation, post-transcriptional alteration by RNA-EDITING, posttranscriptional-regulation of gene-expression and chromatin-remodeling by noncoding or non-messenger RNA- genes consisting of sncRNAs such as microRNAs for inhibiting targeted mRNA including onco-miRNAs, isomirs, oncopharmaco-miRNAs,oncoepi-miRNAs, oncotargo-miRNAs, and siRNAs, lncRNA or  PIWI-RNAs  which may be regulated genomically and epigenomically , DNA-methylation including CpG-islands, shores, shells, promoter-methylation, SINE & LINE-methylation, chromatin-readers, chromatin-folding proteins, such as SATB-1, etc. By using all these, we can regulate oncogene or oncomir addiction, synthetic-lethality, etc.   
Epidrugs which may prove to be very efficient against cancer include chromatin-modifying epidrugs including DNA-methylation(DNMT1) inhibitors and histone-deacetylase(HDAC) inhibitors which may reactivate transcriptionally the expression of noncoding-RNA genes and protein-coding genes, histone-demethylase (HDT) inhibitors, histone-acetyltransferase (HAT) inhibitors, histone-methyltransferase (HMT) inhibitors, regulators of Polycomb protein-group, epitranscriptomic-regulation of RNA-modifications mediated by epigenomic-readers, epigenomic-erasers, epigenomic-writers, epigenomic insulators, shapers or movers,  inhibitors of chromatin-readers including bromodomains and Extra-Terminal Motif-inhibitors, chromosome-remodeling agents targeting nucleosome-sliding and nucleosome-reconstitution, forward and reverse epipharmacogenomics, miRNA-mimics, miRNA-antagonists such as antagomirs, antisense RNA-oligonucleotides, locked nucleic-acids, PNA-antagomirs,  antimiRNA-oligos, miRNA-sponges, miRNA-agomirs, block-miRNAs, replacement-therapies, aptamers, epigenomic-editing, A to I RNA-editing via ADAR, RNAi, modulators of gene-regulatory networks, CRISP GENOME-EDITING, etc.   
Clinical-molecular diagnostic-methods which may be used consist of Bisulfite-sequencing, DNA-methylation analysis, Oxidative-Bisulfite Seq, MRE-sequencing, MBD-sequencing, WGBS-methyl sequencing, OXBS sequencing, ChIP exo, Methyl CpG-Binding domain-sequencing, MeDip-DNA-immunoprecipitation, MS/HMR-analysis, Methylation-specific PCR,  or MSP, DNA-methylation microarray-analysis, bisulfite-sequencing PCR-analysis, LC/MS-MS, Chip-sequencing, epitranscriptomic-sequencing with MeRIP-sequencing and m6A-sequencing, third next-generation REAL TIME-sequencing, MNase sequencing, DNase-sequencing, FAIRE- sequencing, smRNA-sequencing, mRNA-sequencing, etc.     
The future potential of multiomic-based treatments which can be delivered to cellular and molecular targets by nanomedicine-systems shall be taken from lab to clinic by the implementation of Translational Medicine for tailoring personalized, and precision medicine approaches.  Nanodelivery systems may transport therapeutic molecular agents to the targeted tissues, cells, and molecules by circumventing biological milieu interactions and avoiding RES elimination enhancing therapeutic index, while reducing and eliminating systemic toxicity. This way, we can circumvent in the future the traditional-medicine approach of one size fits all or block buster policy, and proceed to the implementation of stratified or precision-medicine, and personalized-medicine for each cancer patient based on multiomic-evidence improving screening, diagnosis, prevention, prognosis, monitoring and mainly treatment of currently incurable tumors. Emphasis should be given to the prevention of solid and liquid cancer development which may be feasible by reversing epigenomic alterations. According to the quote of the ancient Greek-physician Hippocrates who is the father of modern-medicine, “PREVENTION IS ALWAYS BETTER THAN CURE”.

Recently, nanotechnology has garnered enormous atten-tiveness in medicine, as it addresses numerous issues associated with the conventional therapeutic strategies such as poor pharmacokinetics, lack of targeting ability, and system-ic toxicity. Nanoparticles-based formulations have been utilized in various areas of biomedicine, which are of particular interest in drug delivery, imaging and diagnostic platforms, implants, vaccines, and tissue engineering due to their attractive physicochemical properties and biocompatibility. Herein, this article focuses on the insights concerning the impact of nanotechnology on the development of pharmaceutical products, which will emerge as a next-generation therapeutic platform and are envisioned to have a potential impact on public health. In addition, we highlight the existing challenges and prospects for their translation from bench to clinical practice.

Novel drug delivery systems are developed to improve the biological behavior of poorly soluble drugs and to improve therapeutic outcomes. In melanoma therapy, the goal is efficient drug delivery and mitigation of drug resistance. Melphalan (Mel), a currently used therapeutic agent for melanoma, requires solvent system for solubilization, leading to poor chemical stability. Moreover, drug resistance often renders the drug inefficient in clinical setting. A novel β-cyclodextrin-modified gemini surfactant (CDgemini) delivery system was developed to incorporate Mel in order to improve its physicochemical and biological behavior. Melphalan nanoparticles (Mel-NP) showed optimal particle size in the 200-250 nm range for endocytosis and induced significantly higher cell death compared with Mel (50% of inhibitory concentration [IC50] of 36 µM for the complexes vs 82 µM for Mel). The CDgemini delivery system did not alter the pathway of the cellular death triggered by Mel and caused no intrin...

20-(S)-Camptothecin (CPT)-conjugated dipeptides are reported that preassemble into nanotubes with diameters ranging from 80-120 nm. These nanoassemblies maintain a high (~47 %) drug loading and exhibit greater drug stability (i.e., resistance to lactone hydrolysis), and consequently greater efficacy against several human cancer cells (HT-29, A549, H460, and H23) in vitro compared with the clinically used prodrug irinotecan. A key and defining feature of this system is the use of the CPTconjugated dipeptide as both the drug and precursor to the nanostructured carrier, which simplifies the overall fabrication process.

There is increasing interest in developing novel coatings to enhance the biocompatibility of medical implants. A key issue in biocompatibility research is platelet activation and aggregation on the biomaterials' surface. Stoichiometric and nonstoichiometric titanium nitride (TiN x ) films were developed by sputtering as case study materials, for probing platelet activation behavior onto them. Atomic force microscopy (AFM) facilitates the real-time studies of cells and guarantees cellular viability. In this work a methodology for platelets study by AFM was developed. The morphological, structural, optical, and wettability properties of the TiN x films were obtained by AFM, x-ray diffraction, spectroscopic ellipsometry, and contact angle measurements.The properties of TiN x films were correlated with their thrombogenicity involving platelets' adhesion, activation and protein clustering mechanisms. It was found that the TiN x films stoichiometry and surface roughness affect the platelet response. The stoichiometric and smoother TiN films promote platelets adhesion and activation.

Ultrasmall superparamagnetic iron oxide (USPIO) particles are maghemite or magnetite nanoparticles currently used as contrast agent in magnetic resonance imaging. The coatings surrounding the USPIO inorganic core play a major role in both the in vitro stability and, over all, USPIO&#39;s in vivo fate. Different physicochemical properties such as final size, surface charge and coating density are key factors in this respect. Up to now no precise structure--activity relationship has been described to predict entirely the USPIOs stability, as well as their pharmacokinetics and their safety. This review is focused on both the classical and the latest available techniques allowing a better insight in the magnetic core structure and the organic surface of these particles. Concurrently, this work clearly shows the difficulty to obtain a complete physicochemical characterization of USPIOs particles owing to their small dimensions, reaching the analytical resolution limits of many commercial...

N RÉ SUMÉ Nanotechnology involves the creation and use of materials and devices at the size scale of intracellular structures and molecules, and involves systems and constructs in the order of ,100 nm. The aim of nanomedicine is the comprehensive monitoring, control, construction, repair, defence, and improvement of human biological systems at the molecular level, using engineered nanodevices and nanostructures that operate massively in parallel at the single-cell level, ultimately to achieve medical benefit. In this review we consider general principles of nanotechnology as applied to nanomedicine (e.g., biomimicry and pseudointelligence). Some applications of nanotechnology to ophthalmology are described (including treatment of oxidative stress; measurement of intraocular pressure; theragnostics; use of nanoparticles to treat choroidal new vessels, prevent scarring after glaucoma surgery, and treat retinal degenerative disease with gene therapy; prosthetics; and regenerative nanomedicine). Nanotechnology will revolutionize our approach to current therapeutic challenges (e.g., drug delivery, postoperative scarring) and will enable us to address currently unsolvable problems (e.g., sight-restoring therapy for patients with retinal degenerative disease). Obstacles to the incorporation of nanotechnology remain, such as safe manufacturing techniques and unintended biological consequences of nanomaterial use. These obstacles are not insurmountable, and revolutionary treatments for ophthalmic diseases are expected to result from this burgeoning field.

In this review, we discuss the use of inorganic nanoparticles, mainly zinc oxide (ZnO) and titanium dioxide (TiO 2 ), for sunscreen applications considering their intrinsic physical properties and the Mie theory. These properties cause, from one side, attenuation of the ultraviolet light by absorption and scattering (dependent on a particle size), which is the purpose sunscreens are designed for, and formation of free radicals (i.e., phototoxicity) during this process-from the other. Particle penetration into skin is also an important issue addressed in this review due to possible adverse effects associated with interaction between nanoparticles and skin living cells.

Nanomedicine is the medical application of materials, devices, or systems in the nanometer scale and is currently undergoing explosive development. Molecular imaging of cancer using nanosized materials comprises an important part in diagnosis, therapy, and drug discovery in medical nanosciences. Radiopharmaceuticals are a key tool of molecular imaging in the field of nuclear medicine. The in vivo administration of radiolabeled nanoparticles (NPs) can provide an accurate biodistribution profile of the nanoformulations, as well as visualization of their route in vivo. Surface modifications of NPs with antibodies, peptides, or other small molecules that bind to tumor cell receptors have resulted in the development of sensitive and specific targeted imaging and diagnostic modalities for in vitro and in vivo applications. Radiometals are the most favorable of all radionuclides for labeling applications and they have the most suitable properties for single-photon emission computed tomography imaging. Indium-111 ( 111 In), specifically, is a readily available gamma-emitting radiometal, which is widely used in clinical practice for diagnosis and/or therapy. Herein, we will overview the latest evolvement on 111 In-labeled nanoparticles for biodistribution assessment and/or imaging evaluation of nanocarriers, as well as therapy in cancer.

Advances in regenerative nanomedicine raise a host of ethical, legal, and social questions that healthcare providers and scientists will need to consider. These questions and concerns include definitions, appropriate applications, dual use, potential risks, regulations, and access. In this chapter, we provide an overview of the questions and concerns and recommend proactive consideration and solutions.

In the present and future, the word innovation refers to the term nanotechnology where everything is possible in this wonder world which scales from 1 to 100 nm which is 1 millionth of a millimeter. Metal Nanoshells are the one such gift by this technology which is a dielectric core material made up of silica covered by thin metals especially gold. Gold nanoshells have the optical properties of colloidal gold nanoparticles and by varying the core diameter and gold layer thickness of the nanoshells, they are finely tuned in a wide spectrum of visible to near infrared regions (NIRregion). The optical properties of the gold nanoshells are due to the Plasmon resonance at the dielectric -gold interface. Thus gold nanoshells are biocompatilble, stable, optically tunable, photoluminescent and finds place in the field of medicine. By which the noble metal nanoshell shows promise application in biomedical imaging, tissue welding, drug delivery systems, therapeutic applications in general and cancer imaging and treatment in particular. In this review we are going to discuss about the optical properties and applications of the silica -gold nanoshells.

Tissue engineering and regenerative medicine are interdisciplinary fields that apply principles of engineering and life sciences to develop biological substitutes, typically composed of biological and synthetic components, that restore, maintain or improve tissue function. Many tissue engineering technologies are still at a laboratory or pre-commercial scale. The short review paper describes the most significant manufacturing and bio-process challenges inherent in the commercialisation and exploitation of the exciting results emerging from the biological and clinical laboratories exploring tissue engineering and regenerative medicine. A three-generation road map of the industry has been used to structure a view of these challenges and to define where the manufacturing community can contribute to the commercial success of the products from these emerging fields. The first-generation industry is characterised by its demonstrated clinical applications and products in the marketplace, the second is characterised by emerging clinical applications, and the third generation is characterised by aspirational clinical applications. The paper focuses on the cost reduction requirement of the first generation of the industry to allow more market penetration and consequent patient impact. It indicates the technological requirements, for instance the creation of three-dimensional tissue structures, and value chain issues in the second generation of the industry. The third-generation industry challenges lie in fundamental biological and clinical science. The paper sets out a road map of these generations to identify areas for research.

In the last century, a wide variety of methods for the production of spherical microspheres (MS) were discovered and tested. Considering that polymeric MS are widely used in industry, as well as in medical and pharmaceutical fields, researchers developed methods that directly produce a large number of homogeneous particles with near-complete conversion of the starting matrix materials. One of the most difficult factors to control for each new MS production method is its ability to produce MS with a minimal variation in size distribution. Such highly uniform particles, which are also termed 'monodisperse', are preferred as their behavior in both in vitro and in vivo systems can be predicted with high accuracy. Monodisperse polymeric MS are, therefore, used as standards for calibration purposes [1] or as packing material for high-performance liquid chromatography columns . They are also preferred as medical drug carriers, as the pathways of inhaled or injected MS through the human body are largely determined by their size . Unwanted and toxic clogging of capillaries can thus be prevented, while on the other hand targeted embolization of tumor vessels is possible. Similarly, particle size determines the speed and profile of drug release from polymeric MS in a major way . Smaller MS exhibit a higher surface-area-to-volume ratio with increased diffusion and/or (surface) degradation in the case of biodegradable MS, resulting in faster drug release compared with larger MS. In general, the more uniform the MS are, the more repeatable the drug incorporation during the production of the MS and the more reproducible the in vitro and in vivo release profiles are. The drug release in such uniform MS can be predicted precisely from the known surface area with respect to the volume and the welldefined diffusion distances and/or degradation speeds. Major challenges for researchers are, therefore, to both optimize the particle size and minimize the particle size distribution variation. Although a huge variety of published methods in the literature promise monodispersity, standards for the term 'monodispersity' are rare and a lack of common parameters makes it hard to estimate the quality of MS made by different methods. This review attempts to define a set of statistical parameters and provide a criterion for monodispersity. Furthermore, a classification of the methods to produce monodisperse MS is proposed, providing, in each case, examples and applications of the produced particles.

Biomineralization is a dynamic, complex, lifelong process by which living organisms control precipitations of inorganic nanocrystals within organic matrices to form unique hybrid biological tissues, for example, enamel, dentin, cementum, and bone. Understanding the process of mineral deposition is important for the development of treatments for mineralizationrelated diseases and also for the innovation and development of scaffolds. This review provides a thorough overview of the up-to-date information on the theories describing the possible mechanisms and the factors implicated as agonists and antagonists of mineralization. Then, the role of calcium and phosphate ions in the maintenance of teeth and bone health is described. Throughout the life, teeth and bone are at risk of demineralization, with particular emphasis on teeth, due to their anatomical arrangement and location. Teeth are exposed to food, drink, and the microbiota of the mouth; therefore, they have developed a high resistance to localized demineralization that is unmatched by bone. The mechanisms by which demineralizationremineralization process occurs in both teeth and bone and the new therapies/technologies that reverse demineralization or boost remineralization are also scrupulously discussed. Technologies discussed include composites with nano-and micron-sized inorganic minerals that can mimic mechanical properties of the tooth and bone in addition to promoting more natural repair of surrounding tissues. Turning these new technologies to products and practices would improve health care worldwide.

Although the definition is arbitrary, industry and governments are clearly beginning to envision nanotechnology's enormous potential. The process of converting basic research in nanotechnology and nanomedicine into 807 RECENT ADVANCES IN BASIC AND CLINICAL NANOMEDICINE

The nanoscale affects all our lives and in many
different areas, including medicine and pharmacy.
The transformation of materials into the nano
dimension changes their physical properties, and is
used in pharmaceutics to develop a new innovative
formulation principle for poorly soluble drugs: the
drug nanocrystals. This article discusses the physics
behind the drug nanocrystals and the changes of
their physical properties, along with the industrially
relevant production technologies. Also discussed are
the benefits and the disadvantages of the various
ways forward with some examples of products
marketed or in the development pipelines.

Neuronanorobotics is the application of medical nanorobots to the human brain. This paper proposes three specific classes of neuronanorobots, named endoneurobots, gliabots and synaptobots, which together can non-destructively map and monitor the structural changes occurring on the 86 x 10 9 neurons and the 2.42 x 10 14 synapses in the human brain, while also recording the synaptic-processed 4.31 x 10 15 spikes/sec carrying electrical functional information processed in the neuronal and synaptic network.

Nanotechnology is expected to be promising in many fields of medical applications, mainly in cancer treatment. While a large number of very attractive exploitations open up for the clinics, regulatory agencies are very careful in admitting new nanomaterials for human use because of their potential toxicity. The very active research on new nanomaterials that are potentially useful in medicine has not been counterbalanced by an adequate knowledge of their pharmacokinetics and toxicity. The different nanocarriers used to transport and release the active molecules to the target tissues should be treated as additives, with potential side effects of themselves or by virtue of their dissolution or aggregation inside the body. Only recently has a systematic classification of nanomaterials been proposed, posing the basis for dedicated modeling at the nanoscale level. The use of in silico methods, such as nano-QSAR and PSAR, while highly desirable to expedite and rationalize the following stages of toxicological research, are not an alternative, but an introduction to mandatory experimental work.

One of the significant purposes of nanotechnology in the field of medical science is the utilization of
nanotechnology in drug delivery to target the tissue for the treatment of disease like diabetes. The biologically
compatible nanoparticles with biological, chemical, physical properties may be useful to enhance and overcome
the limitations which are caused in the use of traditional medicine system by boosting the rate of drug release
,enhancing drug solubility, and improving the diffusion and distribution of drugs. In this review, we have
highlighted on the term diabetes and its different types. Diabetes is becoming an epidemic, more than 366
millions of people around the world are affected. This, article also focuses on the role of nanoparticles in the
management of diabetes also its different types of as well as its applications and uses in the treatment of
diabetes.