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Construction of redox/pH dual stimuli-responsive PEGylated polymeric micelles for intracellular doxorubicin delivery in liver cancer
作者:Hong Yu Yang, Moon-Sun Jang, Guang Hui Gao,c Jung Hee Lee, Doo Sung Lee*
關鍵字:stimuli-responsive, micelles, DOX
論文來源:期刊
具體來源:DOI https://doi.org/10.1039/C5PY01808K
發表時間:2016年

A new type of redox and pH dual-responsive biodegradable polypeptide micelle was developed based on the disulfide-linked methoxy poly(ethylene glycol)-b-poly[2-(dibutylamino)ethylamine-L-glutamate] (mPEG-SS-PNLG) copolymer and applied as an efficient and intelligent carrier to rapidly trigger the intracellular release of doxorubicin (DOX). The mPEG-SS-PNLG was synthesized by a combination of ring-opening polymerization using mPEG-cystamine as a macroinitiator and a side-chain aminolysis reaction. The cumulative release profile of the DOX-loaded mPEG-SS-PNLG (DOX-mPEG-SS-PNLG) micelles indicated a low level of drug release (approximately 25 wt% within 24 h) at pH 7.4, which was significantly accelerated at a lower pH of 5.0 and a higher reducing environment (over 95 wt% in 24 h), demonstrating unambiguous redox/pH dual-responsive controlled drug release capability. An in vitrocytotoxicity test indicated that empty mPEG-SS-PNLG micelles were nontoxic to HepG2 cells up to a tested concentration of 200 μg mL?1. Confocal laser scanning microscopy observations revealed that DOX-loaded mPEG-SS-PNLG micelles efficiently released DOX into human hepatocellular carcinoma HepG2 cells following 24 h of incubation. Importantly, the DOX-loaded mPEG-SS-PNLG micelles significantly increased in vivo therapeutic efficacy toward HepG2 cells in comparison with the free-DOX and control groups. The successful demonstrations indicate that redox and pH dual-responsive mPEG-SS-PNLG micelles are promising candidates for delivering anti-cancer drugs.


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