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      Recent Progress in the Development of Poly(lactic- co-glycolic acid)-Based Nanostructures for Cancer Imaging and Therapy

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          Abstract

          Diverse nanosystems for use in cancer imaging and therapy have been designed and their clinical applications have been assessed. Among a variety of materials available to fabricate nanosystems, poly(lactic- co-glycolic acid) (PLGA) has been widely used due to its biocompatibility and biodegradability. In order to provide tumor-targeting and diagnostic properties, PLGA or PLGA nanoparticles (NPs) can be modified with other functional materials. Hydrophobic or hydrophilic therapeutic cargos can be placed in the internal space or adsorbed onto the surface of PLGA NPs. Protocols for the fabrication of PLGA-based NPs for cancer imaging and therapy are already well established. Moreover, the biocompatibility and biodegradability of PLGA may elevate its feasibility for clinical application in injection formulations. Size-controlled NP’s properties and ligand–receptor interactions may provide passive and active tumor-targeting abilities, respectively, after intravenous administration. Additionally, the introduction of several imaging modalities to PLGA-based NPs can enable drug delivery guided by in vivo imaging. Versatile platform technology of PLGA-based NPs can be applied to the delivery of small chemicals, peptides, proteins, and nucleic acids for use in cancer therapy. This review describes recent findings and insights into the development of tumor-targeted PLGA-based NPs for use of cancer imaging and therapy.

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          Tumor targeting via EPR: Strategies to enhance patient responses

          The tumor accumulation of nanomedicines relies on the enhanced permeability and retention (EPR) effect. In the last 5-10 years, it has been increasingly recognized that there is a large inter- and intra-individual heterogeneity in EPR-mediated tumor targeting, explaining the heterogeneous outcomes of clinical trials in which nanomedicine formulations have been evaluated. To address this heterogeneity, as in other areas of oncology drug development, we have to move away from a one-size-fits-all tumor targeting approach, towards methods that can be employed to individualize and improve nanomedicine treatments. To this end, efforts have to be invested in better understanding the nature, the complexity and the heterogeneity of the EPR effect, and in establishing systems and strategies to enhance, combine, bypass and image EPR-based tumor targeting. In the present manuscript, we summarize key studies in which these strategies are explored, and we discuss how these approaches can be employed to enhance patient responses.
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            Insight into Cellular Uptake and Intracellular Trafficking of Nanoparticles

            Nanoparticle science is rapidly changing the landscape of various scientific fields and defining new technological platforms. This is perhaps even more evident in the field of nanomedicine whereby nanoparticles have been used as a tool for the treatment and diagnosis of many diseases. However, despite the tremendous benefit conferred, common pitfalls of this technology is its potential short and long-term effects on the human body. To understand these issues, many scientific studies have been carried out. This review attempts to shed light on some of these studies and its outcomes. The topics that were examined in this review include the different possible uptake pathways of nanoparticles and intracellular trafficking routes. Additionally, the effect of physicochemical properties of nanoparticle such as size, shape, charge and surface chemistry in determining the mechanism of uptake and biological function of nanoparticles are also addressed.
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              PLGA nanoparticles containing various anticancer agents and tumour delivery by EPR effect.

              As mortality due to cancer continues to rise, advances in nanotechnology have significantly become an effective approach for achieving efficient drug targeting to tumour tissues by circumventing all the shortcomings of conventional chemotherapy. During the past decade, the importance of polymeric drug-delivery systems in oncology has grown exponentially. In this context, poly(lactic-co-glycolic acid) (PLGA) is a widely used polymer for fabricating 'nanoparticles' because of biocompatibility, long-standing track record in biomedical applications and well-documented utility for sustained drug release, and hence has been the centre of focus for developing drug-loaded nanoparticles for cancer therapy. Such PLGA nanoparticles have also been used to develop proteins and peptides for nanomedicine, and nanovaccines, as well as a nanoparticle-based drug- and gene-delivery system for cancer therapy, and nanoantigens and growth factors. These drug-loaded nanoparticles extravasate through the tumour vasculature, delivering their payload into the cells by the enhanced permeability and retention (EPR) effect, thereby increasing their therapeutic effect. Ongoing research about drug-loaded nanoparticles and their delivery by the EPR effect to the tumour tissues has been elucidated in this review with clarity. Copyright © 2010 Elsevier B.V. All rights reserved.
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                Author and article information

                Journal
                Pharmaceutics
                Pharmaceutics
                pharmaceutics
                Pharmaceutics
                MDPI
                1999-4923
                14 June 2019
                June 2019
                : 11
                : 6
                : 280
                Affiliations
                [1 ]College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Muan-gun, Jeonnam 58554, Korea; ktkim0628@ 123456mokpo.ac.kr
                [2 ]College of Pharmacy, Chungnam National University, Daejeon 34134, Korea; jaeyoung@ 123456cnu.ac.kr
                [3 ]College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Korea; ddkim@ 123456snu.ac.kr
                [4 ]Department of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, Korea
                [5 ]College of Pharmacy, Kangwon National University, Chuncheon 24341, Korea
                Author notes
                [* ]Correspondence: insoo.yoon@ 123456pusan.ac.kr (I.-S.Y.); hjcho@ 123456kangwon.ac.kr (H.-J.C.)
                [†]

                These authors are equally contributed to this work.

                Author information
                https://orcid.org/0000-0002-0997-5723
                https://orcid.org/0000-0002-5070-9371
                Article
                pharmaceutics-11-00280
                10.3390/pharmaceutics11060280
                6630460
                31197096
                3413c53f-f35b-4a91-be18-429ca99f2d54
                © 2019 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
                : 14 May 2019
                : 11 June 2019
                Categories
                Review

                cancer,diagnosis,nanoparticle,plga,targeting,therapy
                cancer, diagnosis, nanoparticle, plga, targeting, therapy

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