Glutathione-mediated shedding of PEG layers based on disulfide-linked catiomers for DNA delivery

被引:46
作者
Cai, Xiao-Jun [1 ]
Dong, Hai-Qing [1 ]
Xia, Wen-Juan [1 ]
Wen, Hui-Yun [1 ]
Li, Xue-Quan [1 ]
Yu, Jin-Hai [1 ]
Li, Yong-Yong [1 ]
Shi, Dong-Lu [1 ,2 ]
机构
[1] Tongji Univ, Sch Med, Inst Adv Mat & Nano Biomed, Shanghai 200092, Peoples R China
[2] Univ Cincinnati, Dept Chem & Mat Engn, Cincinnati, OH 45221 USA
基金
中国国家自然科学基金;
关键词
EFFICIENT GENE-TRANSFER; POLY(ETHYLENE GLYCOL); IN-VITRO; TRANSFECTION; MICELLES; COMPLEXES; POLYMERS; CHITOSAN; SYSTEM; CYTOTOXICITY;
D O I
10.1039/c1jm11693b
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
Engineered PEG-detachable catiomers were developed as non-viral gene vectors to detach the PEG layers responsive to the intracellular reducing environment. These catiomers were found to exhibit high DNA binding ability and reduced cytotoxicity, as evidenced in agarose gel electrophoresis and MTT assays. The size of the mPEG-SS-PLL/DNA complexes was around 100 nm with a regular spherical shape, as observed under transmission electron microscopy (TEM). The complexes were stably dispersed in an aqueous medium with 10% serum. However, fast aggregation was observed in the presence of 10 mM glutathione (GSH) due to detachment of the PEG segment via disulfide cleavage. These complexes showed high transfection efficiency in 293T and Hela cells under optimized conditions. The experimental results indicated that the mPEG-SS-PLL catiomers may have promising potential as a non-viral gene vector.
引用
收藏
页码:14639 / 14645
页数:7
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