title: Co-delivery of chemotherapeutic drugs with vitamin E TPGS by porous PLGA nanoparticles for enhanced chemotherapy against multi-drug resistance.
abstract: We report a strategy to make use of poly(lactic-co-glycolic acid) nanoparticle (PLGA NPs) for co-delivery of docetaxel (DTX) as a model anticancer drug together with vitamin E TPGS. The latter plays a dual role as a pore-forming agent in the nanoparticles that may result in smaller particle size, higher drug encapsulation efficiency and faster drug release, and also as a bioactive agent that could inhibit P-glycoprotein to overcome multi-drug resistance of the cancer cells, The DTX-loaded PLGA NPs of 0, 10, 20 and 40% TPGS were prepared by the nanoprecipitation method and then characterized for their size and size distribution, surface morphology, physical status and encapsulation efficiency of the drug in the NPs. All four NPs were found of size ranged 100-120 nm and EE ranged 85-95% at drug loading level around 10%. The in vitro evaluation showed that the 48 h IC50 values of the free DTX and the DTX-loaded PLGA NPs of 0, 10, 20% TPGS were 2.619 and 0.474, 0.040, 0.009 μg/mL respectively, which means that the PLGA NPs formulation could be 5.57 fold effective than the free DTX and that the DTX-loaded PLGA NPs of 10 or 20% TPGS further be 11.85 and 52.7 fold effective than the DTX-loaded PLGA NPs of no TPGS (therefore, 66.0 and 284 fold effective than the free DTX). Xenograft tumor model and immunohistological staining analysis further confirmed the advantages of the strategy of co-delivery of anticancer drugs with TPGS by PLGA NPs.
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China; The Ministry-Province Jointly Constructed Base for State Key Lab - Shenzhen Key Laboratory of Chemical Biology, The Shenzhen Key Lab of Gene and Antibody Therapy, and Division of Life and Health Sciences, Tsinghua University Shenzhen Graduate School, Shenzhen 518055, China.
authors.forename: Huijun
authors.initials: H
authors.lastname: Zhu
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China; The Ministry-Province Jointly Constructed Base for State Key Lab - Shenzhen Key Laboratory of Chemical Biology, The Shenzhen Key Lab of Gene and Antibody Therapy, and Division of Life and Health Sciences, Tsinghua University Shenzhen Graduate School, Shenzhen 518055, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Chen
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China; The Ministry-Province Jointly Constructed Base for State Key Lab - Shenzhen Key Laboratory of Chemical Biology, The Shenzhen Key Lab of Gene and Antibody Therapy, and Division of Life and Health Sciences, Tsinghua University Shenzhen Graduate School, Shenzhen 518055, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zeng
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China; The Ministry-Province Jointly Constructed Base for State Key Lab - Shenzhen Key Laboratory of Chemical Biology, The Shenzhen Key Lab of Gene and Antibody Therapy, and Division of Life and Health Sciences, Tsinghua University Shenzhen Graduate School, Shenzhen 518055, China.
authors.forename: Zhongyuan
authors.initials: Z
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China; The Ministry-Province Jointly Constructed Base for State Key Lab - Shenzhen Key Laboratory of Chemical Biology, The Shenzhen Key Lab of Gene and Antibody Therapy, and Division of Life and Health Sciences, Tsinghua University Shenzhen Graduate School, Shenzhen 518055, China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China; The Ministry-Province Jointly Constructed Base for State Key Lab - Shenzhen Key Laboratory of Chemical Biology, The Shenzhen Key Lab of Gene and Antibody Therapy, and Division of Life and Health Sciences, Tsinghua University Shenzhen Graduate School, Shenzhen 518055, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Wu
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China; The Ministry-Province Jointly Constructed Base for State Key Lab - Shenzhen Key Laboratory of Chemical Biology, The Shenzhen Key Lab of Gene and Antibody Therapy, and Division of Life and Health Sciences, Tsinghua University Shenzhen Graduate School, Shenzhen 518055, China.
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Gao
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China; The Ministry-Province Jointly Constructed Base for State Key Lab - Shenzhen Key Laboratory of Chemical Biology, The Shenzhen Key Lab of Gene and Antibody Therapy, and Division of Life and Health Sciences, Tsinghua University Shenzhen Graduate School, Shenzhen 518055, China.
authors.forename: Jinxie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China; The Ministry-Province Jointly Constructed Base for State Key Lab - Shenzhen Key Laboratory of Chemical Biology, The Shenzhen Key Lab of Gene and Antibody Therapy, and Division of Life and Health Sciences, Tsinghua University Shenzhen Graduate School, Shenzhen 518055, China.
authors.forename: Kewei
authors.initials: K
authors.lastname: Liu
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, China.
authors.forename: Ranyi
authors.initials: R
authors.lastname: Liu
authors.affiliation: Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
authors.forename: Lintao
authors.initials: L
authors.lastname: Cai
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China; The Ministry-Province Jointly Constructed Base for State Key Lab - Shenzhen Key Laboratory of Chemical Biology, 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.
authors.forename: Lin
authors.initials: L
authors.lastname: Mei
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China; The Ministry-Province Jointly Constructed Base for State Key Lab - Shenzhen Key Laboratory of Chemical Biology, 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. Electronic address: chefss@nus.edu.sg.
authors.forename: Si-Shen
authors.initials: SS
authors.lastname: Feng
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002152:Calorimetry, Differential Scanning; D004337:Drug Carriers; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006367:HeLa Cells; D006801:Humans; D019344:Lactic Acid; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D010316:Particle Size; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013818:Thermogravimetry; D014810:Vitamin E / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D004337:Drug Carriers; D014810:Vitamin E; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Biodegradable polymers; Cancer nanotechnology; Controlled release; Molecular biomaterial; Nanomedicine; Pharmaceutical nanotechnology