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      Recent Advancements of Nanomedicine towards Antiangiogenic Therapy in Cancer

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          Abstract

          Angiogenesis is a process of generation of de-novo blood vessels from already existing vasculature. It has a crucial role in different physiological process including wound healing, embryonic development, and tumor growth. The methods by which therapeutic drugs inhibit tumor angiogenesis are termed as anti-angiogenesis cancer therapy. Developments of angiogenic inhibiting drugs have various limitations causing a barrier for successful treatment of cancer, where angiogenesis plays an important role. In this context, investigators developed novel strategies using nanotechnological approaches that have demonstrated inherent antiangiogenic properties or used for the delivery of antiangiogenic agents in a targeted manner. In this present article, we decisively highlight the recent developments of various nanoparticles (NPs) including liposomes, lipid NPs, protein NPs, polymer NPs, inorganic NPs, viral and bio-inspired NPs for potential application in antiangiogenic cancer therapy. Additionally, the clinical perspectives, challenges of nanomedicine, and future perspectives are briefly analyzed.

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          Most cited references158

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          Angiogenesis: an organizing principle for drug discovery?

          Angiogenesis--the process of new blood-vessel growth--has an essential role in development, reproduction and repair. However, pathological angiogenesis occurs not only in tumour formation, but also in a range of non-neoplastic diseases that could be classed together as 'angiogenesis-dependent diseases'. By viewing the process of angiogenesis as an 'organizing principle' in biology, intriguing insights into the molecular mechanisms of seemingly unrelated phenomena might be gained. This has important consequences for the clinical use of angiogenesis inhibitors and for drug discovery, not only for optimizing the treatment of cancer, but possibly also for developing therapeutic approaches for various diseases that are otherwise unrelated to each other.
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            Vascular Endothelial Growth Factor (VEGF) and Its Receptor (VEGFR) Signaling in Angiogenesis: A Crucial Target for Anti- and Pro-Angiogenic Therapies.

            The vascular endothelial growth factor (VEGF) and its receptor (VEGFR) have been shown to play major roles not only in physiological but also in most pathological angiogenesis, such as cancer. VEGF belongs to the PDGF supergene family characterized by 8 conserved cysteines and functions as a homodimer structure. VEGF-A regulates angiogenesis and vascular permeability by activating 2 receptors, VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk1 in mice). On the other hand, VEGF-C/VEGF-D and their receptor, VEGFR-3 (Flt-4), mainly regulate lymphangiogenesis. The VEGF family includes other interesting variants, one of which is the virally encoded VEGF-E and another is specifically expressed in the venom of the habu snake (Trimeresurus flavoviridis). VEGFRs are distantly related to the PDGFR family; however, they are unique with respect to their structure and signaling system. Unlike members of the PDGFR family that strongly stimulate the PI3K-Akt pathway toward cell proliferation, VEGFR-2, the major signal transducer for angiogenesis, preferentially utilizes the PLCγ-PKC-MAPK pathway for signaling. The VEGF-VEGFR system is an important target for anti-angiogenic therapy in cancer and is also an attractive system for pro-angiogenic therapy in the treatment of neuronal degeneration and ischemic diseases.
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              Polymer conjugates as anticancer nanomedicines.

              The transfer of polymer-protein conjugates into routine clinical use, and the clinical development of polymer-anticancer-drug conjugates, both as single agents and as components of combination therapy, is establishing polymer therapeutics as one of the first classes of anticancer nanomedicines. There is growing optimism that ever more sophisticated polymer-based vectors will be a significant addition to the armoury currently used for cancer therapy.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                10 January 2020
                January 2020
                : 21
                : 2
                : 455
                Affiliations
                [1 ]Aavishkar Oral Strips Pvt Ltd., 109/3, IDA, Phase 2, Sector 2, Lane 6, Cherlapally, Hyderabad 500051, India; anubhabrsv@ 123456gmail.com
                [2 ]Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science, Jacksonville, FL 32224, USA; sagarchemistry@ 123456gmail.com
                [3 ]Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, The University of California, Los Angeles (UCLA), Factor Bldg. 10-240, 621 Charles E. Young Dr., Los Angeles, CA 90095, USA
                [4 ]Department of Bioengineering, Rice University, Houston, TX 77030, USA
                Author notes
                [†]

                These authors contribute equally to this work.

                Author information
                https://orcid.org/0000-0002-3082-8269
                https://orcid.org/0000-0001-9883-190X
                https://orcid.org/0000-0002-9404-0024
                https://orcid.org/0000-0002-3625-2272
                Article
                ijms-21-00455
                10.3390/ijms21020455
                7013812
                31936832
                764fcd52-cfe6-40d3-a9e4-282ed6d8caad
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 24 December 2019
                : 08 January 2020
                Categories
                Review

                Molecular biology
                angiogenesis,anti-angiogenesis,nanomedicine,cancer,theranostics
                Molecular biology
                angiogenesis, anti-angiogenesis, nanomedicine, cancer, theranostics

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