title: Redox-responsive micelles self-assembled from dynamic covalent block copolymers for intracellular drug delivery.
abstract: Redox-responsive micelles self-assembled from dynamic covalent block copolymers with double disulfide linkage in the backbone have been developed successfully. The amphiphilic block copolymers PEG-PLA associated with complementary H-bonding sequences can self-assemble into spherical micelles in aqueous media with sizes from 34 nm to 107 nm with different molar mass of PEG and PLA. Moreover, in vitro drug release analyses indicate that reductive environment can result in triggered drug release profiles. The glutathione (GSH) mediated intracellular drug delivery was investigated against HeLa human cervical carcinoma cell line. Flow cytometry and fluorescence microscopy measurements demonstrated that the micelles exhibited faster drug release in glutathione monoester (GSH-OEt) pretreated HeLa cells than that in the nonpretreated cells. Cytotoxicity assay of DOX-loaded micelles indicated the higher cellular proliferation inhibition against 10 mM of GSH-OEt pretreated HeLa cells than that of the nonpretreated ones. These reduction-responsive, biodegradable and biocompatibility micelles could provide a favorable platform to construct excellent drug delivery systems for cancer therapy.
authors: Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
authors: Qinglai
authors: Q
authors: Yang
authors: Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
authors: Lianjiang
authors: L
authors: Tan
authors: Shanghai Key Laboratory of Gastric Neoplasms, Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors: Changyu
authors: C
authors: He
authors: Shanghai Key Laboratory of Gastric Neoplasms, Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors: Bingya
authors: B
authors: Liu
authors: School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
authors: Yuhong
authors: Y
authors: Xu
authors: Shanghai Key Laboratory of Gastric Neoplasms, Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors: Zhenggang
authors: Z
authors: Zhu
authors: Bio-ID Center, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
authors: Zhifeng
authors: Z
authors: Shao
authors: College of Chemistry, Beijing Normal University, Beijing 100875, China; Department of Chemistry, University at Buffalo, State University of New York, Buffalo, NY 14260, United States.
authors: Bing
authors: B
authors: Gong
authors: Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: yumeishen@sjtu.edu.cn.
authors: Yu-Mei
authors: YM
authors: Shen
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D049109:Cell Proliferation; D004220:Disulfides; D004317:Doxorubicin / Q000008:administration & dosage; D004337:Drug Carriers / Q000378:metabolism; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005978:Glutathione / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D006860:Hydrogen Bonding; D051379:Mice; D008823:Micelles; D041681:NIH 3T3 Cells; D010084:Oxidation-Reduction; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D004220:Disulfides; D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; D011092:Polyethylene Glycols; D004317:Doxorubicin; D005978:Glutathione
keywords: Block copolymer; Double disulfide linkage; H-bonding associated units; Redox responsive; Self-assembled micelles