Redox-responsive micelles self-assembled from multi-block copolymer for co-delivery of siRNA and hydrophobic anticancer drug

被引:3
作者
Liu, Benxing [1 ]
Tan, Lianjiang [1 ]
He, Changyu [2 ]
Liu, Bingya [2 ]
Zhu, Zhenggang [2 ]
Gong, Bing [3 ,4 ]
Shen, Yu-Mei [1 ]
机构
[1] Shanghai Jiao Tong Univ, Shanghai Ctr Syst Biomed, Key Lab Syst Biomed, Shanghai 200240, Peoples R China
[2] Shanghai Jiao Tong Univ, Shanghai Key Lab Gastr Neoplasms, Shanghai Inst Digest Surg, Dept Surg,Ruijin Hosp,Sch Med, Shanghai 200025, Peoples R China
[3] Beijing Normal Univ, Coll Chem, Beijing 100875, Peoples R China
[4] Univ Buffalo, Dept Chem, Buffalo, NY 14260 USA
基金
中国国家自然科学基金;
关键词
Amphiphilic; Multi-block copolymer; Drug carrier; Gene; drug dual delivery; AMPHIPHILIC BLOCK-COPOLYMERS; LOW-MOLECULAR-WEIGHT; BRANCHED POLYETHYLENIMINE; COMPLEX MICELLES; NONVIRAL VECTOR; PLASMID DNA; GENE; CYTOTOXICITY; SYSTEMS; NANOPARTICLES;
D O I
10.1007/s00289-018-2600-y
中图分类号
O63 [高分子化学(高聚物)];
学科分类号
070305 ; 080501 ; 081704 ;
摘要
Novel redox-responsive amphiphilic cationic multi-block copolymers PEG(2000)-PLA(3000)-PEI1200-PLA(3000)-PEG(2000) and PEG(2000)-PLA(3000)-PEI1800-PLA(3000)-PEG(2000) were synthesized and self-assembled into micelles for co-delivery of siRNA and hydrophobic doxorubicin (DOX). The chemical structure and molecular weight of the copolymers were characterized by H-1 nuclear magnetic resonance and gel permeation chromatography, respectively. The copolymeric micelles were examined by dynamic light scattering, and their size, zeta potential and critical micelle concentration were determined. The in vitro drug release analyses indicated that reductive environment can trigger the release of DOX and siRNA by breaking the micelles. MTT assay demonstrated that the DOX/siRNA-loaded micelles are capable of inhibiting proliferation of SGC7901 cells. The results of fluorescence microscopy and flow cytometry verify the simultaneous delivery of DOX and siRNA from the nanomicellar particles into SGC7901 cells. The reduction-responsive cationic copolymers will provide a platform for constructing drug/gene delivery system toward cancer therapy.
引用
收藏
页码:4237 / 4257
页数:21
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