Redox-responsive micelles self-assembled from dynamic covalent block copolymers for intracellular drug delivery

Qinglai Yang; Lianjiang Tan; Changyu He; Bingya Liu; Yuhong Xu; Zhenggang Zhu; Zhifeng Shao; Bing Gong; Yu-Mei Shen

doi:10.1016/j.actbio.2015.01.044

Redox-responsive micelles self-assembled from dynamic covalent block copolymers for intracellular drug delivery

Acta Biomater. 2015 Apr:17:193-200. doi: 10.1016/j.actbio.2015.01.044. Epub 2015 Feb 7.

Authors

Qinglai Yang¹, Lianjiang Tan¹, Changyu He², Bingya Liu², Yuhong Xu³, Zhenggang Zhu², Zhifeng Shao⁴, Bing Gong⁵, Yu-Mei Shen⁶

Affiliations

¹ Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
² 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.
³ School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
⁴ Bio-ID Center, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
⁵ 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.
⁶ Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: [email protected].

PMID: 25662913
DOI: 10.1016/j.actbio.2015.01.044

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.

Keywords: Block copolymer; Double disulfide linkage; H-bonding associated units; Redox responsive; Self-assembled micelles.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Biocompatible Materials
Cell Proliferation
Disulfides
Doxorubicin / administration & dosage
Drug Carriers / metabolism
Drug Delivery Systems*
Drug Liberation
Glutathione / chemistry
HeLa Cells
Humans
Hydrogen Bonding
Mice
Micelles
NIH 3T3 Cells
Oxidation-Reduction*
Polyethylene Glycols / chemistry*
Polymers / chemistry*

Substances

Biocompatible Materials
Disulfides
Drug Carriers
Micelles
Polymers
monomethoxypolyethyleneglycol-polylactide block copolymer
Polyethylene Glycols
Doxorubicin
Glutathione