title: Blended nanoparticle system based on miscible structurally similar polymers: a safe, simple, targeted, and surprisingly high efficiency vehicle for cancer therapy.
abstract: A novel blended nanoparticle (NP) system for the delivery of anticancer drugs and its surprisingly high efficacy for cancer chemotherapy by blending a targeting polymer folic acid-poly(ethylene glycol)-b-poly(lactide-co-glycolide) (FA-PEG-b-PLGA) and a miscible structurally similar polymer D-α-tocopheryl polyethylene glycol 1000 succinate-poly(lactide-co-glycolide) (TPGS-PLGA) is reported. This blended NP system can be achieved through a simple and effective nanoprecipitation technique, and possesses unique properties: i) improved long-term compatibility brought by PEG-based polymers; ii) reduced multidrug resistance mediated by P-glycoprotein (P-gp) in tumor cells and increased bioavailability of anticancer drugs by incorporation of TPGS; iii) the regulation of controlled release through polymer ratios and active targeting by FA. Both in vitro cell experiments and in vivo antitumor assays demonstrated the reported blended NP system can achieve the best therapeutic efficiency in an extremely safe, simple and highly efficient process for cancer therapy. Moreover, this NP system is highly efficient in forming NPs with multiple functions, without repeated chemical modification of polymers, which is sometimes complex, inefficient and high cost. Therefore, the development of this novel blended NP concept is extremely meaningful for the application of pharmaceutical nanotechnology in recent studies.
authors: School of Life Sciences, Tsinghua University, Beijing, 100084, P. R. China.|The Shenzhen Key Lab of Gene and Antibody Therapy, Graduate School at Shenzhen, Division of Life and Health Sciences, Tsinghua University, Shenzhen, 518055, P. R. China.|Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
authors: Wei
authors: W
authors: Tao
authors: School of Life Sciences, Tsinghua University, Beijing, 100084, P. R. China.|The Shenzhen Key Lab of Gene and Antibody Therapy, Graduate School at Shenzhen, Division of Life and Health Sciences, Tsinghua University, Shenzhen, 518055, P. R. China.
authors: Jinxie
authors: J
authors: Zhang
authors: School of Life Sciences, Tsinghua University, Beijing, 100084, P. R. China.|The Shenzhen Key Lab of Gene and Antibody Therapy, Graduate School at Shenzhen, Division of Life and Health Sciences, Tsinghua University, Shenzhen, 518055, P. R. China.
authors: Xiaowei
authors: X
authors: Zeng
authors: Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.|Department of Chemistry, University of Waterloo, Waterloo, Ontario, Canada.
authors: Danny
authors: D
authors: Liu
authors: School of Life Sciences, Tsinghua University, Beijing, 100084, P. R. China.|The Shenzhen Key Lab of Gene and Antibody Therapy, Graduate School at Shenzhen, Division of Life and Health Sciences, Tsinghua University, Shenzhen, 518055, P. R. China.
authors: Gan
authors: G
authors: Liu
authors: Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
authors: Xi
authors: X
authors: Zhu
authors: Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
authors: Yanlan
authors: Y
authors: Liu
authors: Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
authors: Qingtong
authors: Q
authors: Yu
authors: School of Life Sciences, Tsinghua University, Beijing, 100084, P. R. China.|The Shenzhen Key Lab of Gene and Antibody Therapy, Graduate School at Shenzhen, Division of Life and Health Sciences, Tsinghua University, Shenzhen, 518055, P. R. China.
authors: Laiqiang
authors: L
authors: Huang
authors: School of Life Sciences, Tsinghua University, Beijing, 100084, P. R. China.|The Shenzhen Key Lab of Gene and Antibody Therapy, Graduate School at Shenzhen, Division of Life and Health Sciences, Tsinghua University, Shenzhen, 518055, P. R. China.
authors: Lin
authors: L
authors: Mei
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001672:Biocompatible Materials / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000077143:Docetaxel; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D005492:Folic Acid / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D016513:Mice, SCID; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000628:therapy*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011098:Polyglactin 910 / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D043823:Taxoids / Q000494:pharmacology; D014810:Vitamin E / Q000737:chemistry
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D011108:Polymers; D043823:Taxoids; C102418:poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer; D014810:Vitamin E; D000077143:Docetaxel; D011100:Polyglycolic Acid; D011098:Polyglactin 910; D011092:Polyethylene Glycols; D005492:Folic Acid; C014225:tocophersolan
keywords: blended nanoparticles; cancer therapy; miscible polymers; multifunctional vehicles; pharmaceutical nanotechnology