First-in-Class Phosphorus Dendritic Framework, a Wide Surface Functional Group Palette Bringing Noteworthy Anti-Cancer and Anti-Tuberculosis Activities: What Lessons to Learn?

Based on phenotypic screening, the major advantages of phosphorus dendrimers and dendrons as drugs allowed the discovery of new therapeutic applications, for instance, as anti-cancer and anti-tuberculosis agents. These biological activities depend on the nature of the chemical groups (neutral or cationic) on their surface as well as their generation. As lessons to learn, in the oncology domain, the increase in the generation of metallo-dendrimers is in the same direction as the anti-proliferative activities, in contrast to the development of polycationic dendrimers, where the most potent anti-tuberculosis phosphorus dendrimer was observed to have the lowest generation (G0). The examples presented in this original analysis of phosphorus dendrimers and dendrons provide support for the lessons learned and for the development of new nanoparticles in nanomedicine.

Advances in Nanodelivery of Green Tea Catechins to Enhance the Anticancer Activity.

Cancer is one of the leading causes of death globally. A variety of phenolic compounds display preventative and therapeutic effects against cancers. Green teas are rich in phenolics. Catechins are the most dominant phenolic component in green teas. Studies have shown that catechins have anticancer activity in various cancer models. The anticancer activity of catechins, however, may be compromised due to their low oral bioavailability. Nanodelivery emerges as a promising way to improve the oral bioavailability and anticancer activity of catechins. Research in this area has been actively conducted in recent decades. This review provides the molecular mechanisms of the anticancer effects of catechins, the factors that limit the oral bioavailability of catechins, and the latest advances of delivering catechins using nanodelivery systems through different routes to enhance their anticancer activity.

Nanoceutical Adjuvants as Wound Healing Material: Precepts and Prospects.

Dermal wound healing describes the progressive repair and recalcitrant mechanism of 12 damaged skin, and eventually, reformatting and reshaping the skin. Many probiotics, nutritional supplements, metal nanoparticles, composites, skin constructs, polymers, and so forth have been associated with the improved healing process of wounds. The exact mechanism of material-cellular interaction is a point of immense importance, particularly in pathological conditions such as diabetes. Bioengineered alternative agents will likely continue to dominate the outpatient and perioperative management of chronic, recalcitrant wounds as new products continue to cut costs and improve the wound healing process. This review article provides an update on the various remedies with confirmed wound healing activities of metal-based nanoceutical adjuvanted agents and also other nano-based counterparts from previous experiments conducted by various researchers.

Functionalized Reduced Graphene Oxide as a Versatile Tool for Cancer Therapy.

Cancer is one of the deadliest diseases in human history with extremely poor prognosis. Although many traditional therapeutic modalities-such as surgery, chemotherapy, and radiation therapy-have proved to be successful in inhibiting the growth of tumor cells, their side effects may vastly limited the actual benefits and patient acceptance. In this context, a nanomedicine approach for cancer therapy using functionalized nanomaterial has been gaining ground recently. Considering the ability to carry various anticancer drugs and to act as a photothermal agent, the use of carbon-based nanomaterials for cancer therapy has advanced rapidly. Within those nanomaterials, reduced graphene oxide (rGO), a graphene family 2D carbon nanomaterial, emerged as a good candidate for cancer photothermal therapy due to its excellent photothermal conversion in the near infrared range, large specific surface area for drug loading, as well as functional groups for functionalization with molecules such as photosensitizers, siRNA, ligands, etc. By unique design, multifunctional nanosystems could be designed based on rGO, which are endowed with promising temperature/pH-dependent drug/gene delivery abilities for multimodal cancer therapy. This could be further augmented by additional advantages offered by functionalized rGO, such as high biocompatibility, targeted delivery, and enhanced photothermal effects. Herewith, we first provide an overview of the most effective reducing agents for rGO synthesis via chemical reduction. This was followed by in-depth review of application of functionalized rGO in different cancer treatment modalities such as chemotherapy, photothermal therapy and/or photodynamic therapy, gene therapy, chemotherapy/phototherapy, and photothermal/immunotherapy.

Issues affecting nanomedicines on the way from the bench to the market.

The development of innovative nanomedicine has raised the standards over the last few decades. The establishment of research institutes with robust budgets dedicated to nanomedicine has created promise for the development of products based on biomedical applications of nanotechnology. Currently, this development meets obstacles because some of the scientific community has raised concerns regarding the launch of nanomedicine in the market. In this review highlight, we aimed to discuss some of these concerns and contribute to this discussion. For this purpose, we enumerated three issues that should be deeply discussed by the nanotech community to improve the translation of innovation from the laboratory to the market: (1) set-up more effective scaled-up industrial processes; (2) correlate data from preclinical and clinical studies with nanomedical developments; (3) optimize the incorporation of nanoparticles in a compatible final pharmaceutical form. Other issues are also important for this discussion, but we believe that these three are fundamental aspects to bridge the gap between basic nanoscience knowledge to market nanomedical innovations.

Nanomedicine: a new paradigm to overcome drug incompatibilities.

OBJECTIVES: Drug incompatibilities may compromise the safety and effectiveness of combined drugs and result in mild-to-serious clinical complications, such as catheter obstruction, loss of drug efficacy, formation of toxic derivatives and embolism. Various preventive strategies have been implemented to overcome drug incompatibilities with limited success. This review presents an innovative approach to prevent drug incompatibilities via isolating the incompatible drugs into nanostructures. KEY FINDINGS: Several examples of incompatible drugs may be loaded separately into nanostructures of various types. Physicochemical characteristics and biocompatibility of the nanomaterials that are being utilized to prevent physicochemical incompatibilities should be carefully considered. CONCLUSIONS: There is a new era of exploiting nanomaterials in overcoming various types of physicochemical incompatibilities, with additional benefits of further improvements in pharmacokinetic profiles and pharmacological actions of the administered drugs.

Above and Beyond Cancer Therapy: Translating Biomaterials into the Clinic.

Given extensive reports of anticancer nanomedicines in preclinical studies, why is there such a paucity of clinical trials using these therapies? Nanotechnology can certainly deliver, but we need to tackle the limitations that are impeding the translation of nanomedicines into the clinic and start benefiting from their full potential.

Factors influencing safety and efficacy of intravenous iron-carbohydrate nanomedicines: From production to clinical practice.

Iron deficiency is an important subclinical disease affecting over one billion people worldwide. A growing body of clinical records supports the use of intravenous iron-carbohydrate complexes for patients where iron replenishment is necessary and oral iron supplements are either ineffective or cannot be tolerated by the gastrointestinal tract. A critical characteristic of iron-carbohydrate drugs is the complexity of their core-shell structure, which has led to differences in the efficacy and safety of various iron formulations. This review describes parameters influencing the safety and effectiveness of iron-carbohydrate complexes during production, storage, handling, and clinical application. We summarized the physicochemical and biological assessments of commercially available iron carbohydrate nanomedicines to provide an overview of publicly available data. Further, we reviewed studies that described how subtle differences in the manufacturing process of iron-carbohydrate complexes can impact on the physicochemical, biological, and clinical outcomes of original product versus their intended copies or so-called iron "similar" products.

A Review on the Scope of Photothermal Therapy-Based Nanomedicines in Preclinical Models of Colorectal Cancer.

Oncologic thermal ablation involves the use of hyperthermic temperatures to damage and treat solid cancers. Thermal ablation is being investigated as a method of treatment in colorectal cancers and has the potential to complement conventional anticancer treatments in managing local recurrence and metastatic disease. Photothermal therapy utilizes photosensitive agents to generate local heat and induce thermal ablation. There is growing interest in developing nanotechnology platforms to deliver such photosensitive agents. An advantage of nanomedicines is their multifunctionality, with the capability to deliver combinations of chemotherapeutics and cancer-imaging agents. To date, there have been no clinical studies evaluating photothermal therapy-based nanomedicines in colorectal cancers. This review presents the current scope of preclinical studies, investigating nanomedicines that have been developed for delivering multimodal photothermal therapy to colorectal cancers, with an emphasis on potential clinical applications.

Therapeutic applications of selenium nanoparticles.

Nanoparticles (NPs) serve to reduce the toxicity, enhance bioactivity, improve targeting, and provide versatile means to control the release profile of the encapsulated moiety. Among different NPs, inorganic NPs of metals like Ag, Au, Ce, Fe, Se, Ti and Zn possess a significant place owing to their unique bioactivities in nanoforms. Selenium (Se) is an essential trace element. It is incorporated into selenoproteins as selenocysteine (Sec) representing the most important part of the active center of their enzymatic activities. Many selenoproteins have oxidoreductase activity and, thus, regulate the physiological redox balance. Se has a narrow therapeutic window and the toxicity margins are very delicate whereas the nanoparticles of Se (SeNPs) possess remarkably reduced toxicity. SeNPs have been explored in various oxidative stress and inflammation mediated disorders like arthritis, cancer, diabetes and nephropathy with potential therapeutic benefits. SeNPs constitute an attractive carrier platform to ferry various drugs to the site of action. Herein we have discussed the significance of nanosizing on the pharmacological activity of Se. The role of SeNPs in pharmacological protection against various inflammatory and oxidative stress mediated conditions is presented. However, it is largely unknown how SeNPs may affect the pharmacokinetics and pharmacodynamics of selenoproteins. Most of the available studies were poorly designed without any comparison to the other Se sources. In the future, detailed studies with inclusion of an appropriate source of Se should be carried out with emphasis on understanding the role of selenoproteins in the observed pharmacological activity.

Homeopathy Seen as Personalised Nanomedicine.

Among all the discoveries of Hahnemann, potentisation was the most important, though controversial. The curative effect of individualised homeopathic potencies is empirical but inexplicable by the conventional principles of science. This paradox is a highly contentious topic of debate between rationalists and homeopaths. Recent discoveries relating to the nano-particulate nature of homeopathic ultra-high potencies and their potential effect on individual gene expression give new insights into this complex issue. It is concluded that homeopathy may be viewed as 'personalised nanomedicine'.

The promising future of nano-antioxidant therapy against environmental pollutants induced-toxicities.

Developmental toxicity caused by exposure to a mixture of environmental pollutants has become a major health concern. Human-made chemicals, including xenoestrogens, pesticides, heavy metals, polycyclic aromatic hydrocarbons (PAHs) are major factors that increase formation of Reactive Oxygen Species (ROS) and adversely influence endogen antioxidant defense. Humans have evolved complex antioxidants systems that protect cells from prooxidant conditions. Deficiency of any these components can cause destruction in the overall antioxidant status of an individual. Antioxidants agents can be endogenous or obtained exogenously, as a part of a diet or through dietary supplements. Although oxidative damage contributes to many pathologies the use of naturally occurring, small-molecule exogenous antioxidants as therapies for these disorders has not been successful. An ideal exogenous antioxidant should be readily absorbed, enough delivered to intracellular location required to decrease pathological oxidative damage, positively affecting gene expression. To develop effective antioxidant therapies the best strategy may be to create new nanoscale drug delivery systems. This review highlights the role of environmental induced oxidative stress factors and novel nanoparticle design techniques of antioxidants.

Improving on Nature: The Role of Nanomedicine in the Development of Clinical Natural Drugs.

Natural products have been used as a major source of drugs for millennia, and about half of the pharmaceuticals in use today are derived from natural products. However, their efficacy can be limited because of their low hydrophilicity and intrinsic dissolution rate(s), or physical/chemical instability. In addition, they can present scarce absorption, poor pharmacokinetics and bioavailability, scarce biodistribution, first-pass metabolism, trivial penetration and accumulation in the organs of the body, or low targeting efficacy. Novel nanoformulations based on drug delivery systems, namely nanoparticles, micelles, and vesicles, offer significant promise in overcoming these limitations. Nowadays, nanomedicine is crucial in developing appropriate therapeutic treatments of essential drugs, specifically antitumor and antiparasistic agents (i.e., Taxol, vincristine, camptothecin, doxorubicin, artemisinin) and other emerging molecules with pleiotropic functions (i.e., resveratrol, curcumin, salvianolic acid B, honokiol). Additionally, the number of nanoformulations developed with flavonoids, in particular rutin, quercetin, silymarin, and green tea catechins, is constantly increasing, and a significant number of publications have appeared in the last decade pertaining to nanoformulations based on extracts and essential oils. Most of these studies report very promising nanoformulations with sustained release and improved bioavailability at much lower doses than conventional preparations, and in many cases, also a better safety profile.

Prospects of Bacteriotherapy with Nanotechnology in Nanoparticledrug Conjugation Approach for Cancer Therapy.

Bacteriotherapy and nanotechnology have shown remarkable potential in diagnostic and therapeutic applications for various diseases. Individual impacts of these micro-nano systems over different aspects of human health are well studied; however, an integrated system of bacteria-nanoparticle (NP) conjugation is less explored. The untamed potential of bacteria-NP conjugation could be a new tool for diagnosis and treatment of invasive diseases like malaria, tuberculosis and cancer. Mammalian cells exhibit cytosis as their defense mechanism when they encounter foreign elements such as bacteria. In these mammalian cells, during phagocytosis, bacteria are ruptured and lysed by lysozymes. A bacterium carrying the drug-tagged NP would be engulfed in the same manner and ultimately reaches the target cells. Rapid and continuous cell divisions in the cancer tissues lead to defective vessels, underdeveloped cellcell interconnects, development of hypoxic areas and heterogeneous population of tumor cells. This unorganized and poorly developed angiogenesis in tumor cells makes it difficult for conventional chemotherapeutic drugs to localize the tumors selectively. In the present scenario of diagnosis and treatment of cancer/tumor cells, it could be expected that the existing bacteriotherapy with the advanced nanotechnology would be a way further in the targeted drug delivery for cancer therapy. This review emphasizes the potential applications of bacteriotherapy with nanotechnology for the diagnosis and treatment of cancer.

Advancements and Avenues in Nanophytomedicines for Better Pharmacological Responses.

Novel drugs delivery systems (NDDS), formulations from plant actives and extracts are still a matter of thrust and hot cake among the researchers working with phytomedicine. Novel delivery systems such as polymeric liposomes, colloidisomes, aquasomes, ethosomes, niosomes, proliposomes, phytosomes, nanoparticles, nanocapsules, nanoemulsions, microsphere and transferosomes have been proven to be a better carrier for delivery of the phyto-constituents as already done by various eminent scientists. Due to increased bioavailability, protection from toxicity, enhancement of pharmacological activity, enhancement of stability, improved tissue macrophages distribution, sustained delivery, and protection from physical and chemical degradation novel delivery systems are more suitable delivery system in compare to the conventional systems. This articled, highlight the remarkable findings in the recent past by innovators exclusively working on novel drug delivery systems for phyto-constituents.

The emerging applications of magnetic nanovectors in nanomedicine.

The scientific disciplines that encompass medical therapy and diagnostics, in a continuing transition to personalized medicine, have found a valuable tool in the emerging field of nanotechnology. New nanotools are now enabling discoveries and advancements that form the foundation of what has become known collectively as nanomedicine. The global impact of these advancements are being seen in areas of advanced/improved early stage diagnostics, targeted drug delivery systems and imaging methods, all leading to more effective diagnostic/therapeutic strategies and outcomes. This review focuses on recent patent advancements in this transition with emphasis on the emerging role of magnetic nanovectors as enabling tools for the enhanced effectiveness of cancer diagnostics and therapeutics, considering its historical progression and future impact.

Combinatorial screening for specific drug solubilizers with switchable release profiles.

Polymer-block-peptide conjugates are tailored to render hydrophobic small molecule drugs water soluble. The combinatorial strategy selects for bioconjugates that exhibit sequence-specific solubilization and switchable release profiles of the cargo through incorporation of a disulfide linker moiety into the peptide-library design. While the study focused on the photosensitizer m-THPC and reductive carrier cleavage, the approach is generic and might be expanded toward a broad range of poorly soluble small-molecule drugs and other selective cleavage mechanisms to disassemble a peptide binding domain of the bioconjugate-based solubilizer.

Nanotechnology and antioxidant therapy: an emerging approach for neurodegenerative diseases.

The efficacy, cellular uptake and specific transport of dietary antioxidants to target organs, tissues and cells remains the most important setback for their application in the treatment of oxidative-stress related disorders and in particular in neurodegenerative diseases, as brain targeting remains a still unsolved challenge. Nanotechnology based delivery systems can be a solution for the above mentioned problems, specifically in the case of targeting dietary antioxidants with neuroprotective activity. Nanotechnology-based delivery systems can protect antioxidants from degradation, improve their physicochemical drug-like properties and in turn their bioavailability. The impact of nanomedicine in the improvement of the performance of dietary antioxidants, as protective agents in oxidative- stress events, specifically through the use of drug delivery systems, is highlighted in this review as well as the type of nanomaterials regularly used for drug delivery purposes. From the data one can conclude that the research combining (dietary) antioxidants and nanotechnology, namely as a therapeutic solution for neurodegenerative diseases, is still in a very early stage. So, a huge research area remains to be explored that hopefully will yield new and effective neuroprotective therapeutic agents in a foreseeable future.

Cancer nanomedicine: from drug delivery to imaging.

Nanotechnology-based chemotherapeutics and imaging agents represent a new era of "cancer nanomedicine" working to deliver versatile payloads with favorable pharmacokinetics and capitalize on molecular and cellular targeting for enhanced specificity, efficacy, and safety. Despite the versatility of many nanomedicine-based platforms, translating new drug or imaging agents to the clinic is costly and often hampered by regulatory hurdles. Therefore, translating cancer nanomedicine may largely be application-defined, where materials are adapted only toward specific indications where their properties confer unique advantages. This strategy may also realize therapies that can optimize clinical impact through combinatorial nanomedicine. In this review, we discuss how particular materials lend themselves to specific applications, the progress to date in clinical translation of nanomedicine, and promising approaches that may catalyze clinical acceptance of nano.