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      Recent advances in anti-angiogenic nanomedicines for cancer therapy

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          Abstract

          The controlled delivery of nanomedicine-based antiangiogenic inhibitors or chemotherapeutics can revitalize therapeutic success by vessel normalization.

          Abstract

          Angiogenesis is a normal physiological remodeling process initiated at the time of embryonic development and lessened with the progress of time. Nevertheless, continuous activation of stringent signaling pathways and proangiogenic factors during tumorigenesis (a pathological condition) instigates serious vessel abnormalities eliciting severe therapeutic inefficiency. In principle, systemic delivery of robust antiangiogenic drugs often fails to reach these abnormal tumor vessels depicting poor pharmacokinetics, biodistribution profiles and adverse side effects in vivo. Recently, the advent of nanotechnology has offered numerous advantages encompassing high drug payloads, increased blood half-life and reduced toxicity; likewise, such nanomedicines can also target the key components of the tumor microenvironment and tumor cells effectively. Synergistic targeting of malignant cells and vessel abnormalities via integration of antiangiogenic and other potent combinational regimens in a single nanoplatform can revitalize therapeutic success. In this review, we will discuss the most promising nanotechnological advancements rehabilitating angiogenesis, and emerging nanocarriers comprehending gene delivery, stem cell therapies and dynamic combinational strategies for effective anticancer therapy.

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          Analysis of nanoparticle delivery to tumours

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            Knocking down barriers: advances in siRNA delivery

            Key Points RNA interference (RNAi) is a fundamental pathway in eukaryotic cells by which sequence-specific small interfering RNA (siRNA) is able to silence genes through the destruction of complementary mRNA. RNAi is an important therapeutic tool that can be used to silence aberrant endogenous genes or to knockdown genes essential to the proliferation of infectious organisms. Delivery remains the central challenge to the therapeutic application of RNAi technology. Before siRNA can take effect in the cytoplasm of a target cell, it must be transported through the body to the target site without undergoing clearance or degradation. Currently, the most effective synthetic, non-viral delivery agents of siRNA are lipids, lipid-like materials and polymers. Various cationic agents including stable nucleic acid–lipid particles, lipidoids, cyclodextrin polymers and polyethyleneimine polymers have been used to achieve the successful systemic delivery of siRNA in mammals without inducing significant toxicity. Direct conjugation of delivery agents to siRNA can facilitate delivery. For example, cholesterol-modified siRNA enables targeting to the liver. RNAi therapeutics have progressed to the clinic, where studies are being conducted to determine siRNA efficacy in treating several diseases, including age-related macular degeneration and respiratory syncytial virus. Moving forward, it will be important to pay close attention to the potential nonspecific immunostimulatory effects of siRNA. Modifications to siRNA can be used to minimize stimulation of the immune system, and an increased emphasis must be placed on performing proper controls to ensure that therapeutic effects are sequence-specific.
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              Molecular regulation of vessel maturation.

              The maturation of nascent vasculature, formed by vasculogenesis or angiogenesis, requires recruitment of mural cells, generation of an extracellular matrix and specialization of the vessel wall for structural support and regulation of vessel function. In addition, the vascular network must be organized so that all the parenchymal cells receive adequate nutrients. All of these processes are orchestrated by physical forces as well as by a constellation of ligands and receptors whose spatio-temporal patterns of expression and concentration are tightly regulated. Inappropriate levels of these physical forces or molecules produce an abnormal vasculature--a hallmark of various pathologies. Normalization of the abnormal vasculature can facilitate drug delivery to tumors and formation of a mature vasculature can help realize the promise of therapeutic angiogenesis and tissue engineering.
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                Author and article information

                Journal
                NANOHL
                Nanoscale
                Nanoscale
                Royal Society of Chemistry (RSC)
                2040-3364
                2040-3372
                2018
                2018
                : 10
                : 12
                : 5393-5423
                Affiliations
                [1 ]Department of Biomedical Engineering
                [2 ]College of Engineering
                [3 ]Peking University
                [4 ]Beijing 100871
                [5 ]China
                Article
                10.1039/C7NR09612G
                29528075
                853958e2-bbe3-4ba6-98de-2b6f4fca15ed
                © 2018

                http://rsc.li/journals-terms-of-use

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