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      The chemotherapeutic potential of PEG-b-PLGA copolymer micelles that combine chloroquine as autophagy inhibitor and docetaxel as an anti-cancer drug.

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          Abstract

          Micelles may be the nanocarrier that is used most often in the area of nanomedicine due to its promising performance and technical simplicity. However, like the original drugs, micellar formulation may arouse intracellular autophagy that deteriorates their advantages for efficient drug delivery. There has been no report in the literature that involves the fate of micelles after successfully internalized into the cancer cells. In this study, we show by using docetaxel-loaded PEG-b-PLGA micelles as a micellar model that the micelles do arouse intracellular autophagy and are thus subject to degradation through the endo-lysosome pathway. Moreover, we show that co-administration of the micellar formulation with autophagy inhibitor such as chloroquine (CQ) could significantly enhance their therapeutic effects. The docetaxel-loaded PEG-b-PLGA micelles are formulated by the membrane dialysis method, which are of 7.1% drug loading and 72.8% drug encapsulation efficiency in a size range of around 40 nm with narrow size distribution. Autophagy degradation and inhibition are investigated by confocal laser scanning microscopy with various biological makers. We show that the IC50 values of the drug formulated in the PEG-b-PLGA micelles after 24 h treatment MCF-7 cancer cells with no autophagy inhibitor or in combination with CQ were 22.30 ± 1.32 and 1.75 ± 0.43 μg/mL respectively, which indicated a 12-fold more efficient treatment with CQ. The in vivo investigation further confirmed the advantages of such a strategy. The findings may provide advanced knowledge for development of nanomedicine for clinical application.

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          Author and article information

          Journal
          Biomaterials
          Biomaterials
          1878-5905
          0142-9612
          Nov 2014
          : 35
          : 33
          Affiliations
          [1 ] School of Life Sciences, Tsinghua University, Beijing 100084, China; The Shenzhen Key Lab of Gene and Antibody Therapy, and Division of Life and Health Sciences, Tsinghua University Shenzhen Graduate School, Shenzhen 518055, China.
          [2 ] Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, University of Chinese Academy of Sciences, Guangzhou, Guangdong 510530, China.
          [3 ] School of Life Sciences, Tsinghua University, Beijing 100084, China; The Shenzhen Key Lab of Gene and Antibody Therapy, and Division of Life and Health Sciences, Tsinghua University Shenzhen Graduate School, Shenzhen 518055, China. Electronic address: mei.lin@sz.tsinghua.edu.cn.
          [4 ] School of Life Sciences, Tsinghua University, Beijing 100084, China; The Shenzhen Key Lab of Gene and Antibody Therapy, and Division of Life and Health Sciences, Tsinghua University Shenzhen Graduate School, Shenzhen 518055, China; Department of Chemical & Biomolecular Engineering, National University of Singapore, Block E5, 02-11, 4 Engineering Drive 4, Singapore 117576, Singapore; International Joint Cancer Institute, The Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433, China. Electronic address: chefss@nus.edu.sg.
          Article
          S0142-9612(14)00837-0
          10.1016/j.biomaterials.2014.07.028
          25109439
          3cc507bb-1ce8-4ab1-b782-2c6d74170655
          Copyright © 2014 Elsevier Ltd. All rights reserved.
          History

          Biodegradable polymers,Cancer nanotechnology,Chemotherapeutic engineering,Intracellular autophagy,Nanomedicine,Pharmaceutical nanotechnology

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