期刊
MOLECULAR PHARMACEUTICS
卷 13, 期 6, 页码 1750-1762出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.5b00696
关键词
redox-sensitive; polymeric micelle; triggered intracellular delivery; paclitaxel; anticancer effects
资金
- National Natural Science Foundation of China [81102397, 81573613]
- Natural Science Foundation of Jiangsu Province [BK2012761, BK20130655]
- Qing Lan Project of Jiangsu Province [02432009]
- Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University [JKPZ2013004]
- Open Fund of State Key Laboratory of Natural Medicines [SKLNMKF201612]
- Major Program for the Fundamental Research of Shanghai Committee of Science and Technology, China [14JC1491300]
A redox-sensitive micellar system constructed from an O,N-hydroxyethyl chitosan octylamine (HECS-ss-OA) conjugate with disulfide linkages between the hydrophobic alkyl chains and hydrophilic chitosan backbone was synthesized for triggered intracellular delivery of hydrophobic paclitaxel (PTX). In aqueous environments, conjugates formed micelles with high PTX loading (>30%). Mechanistically, the sensitivity of HECS-ss-OA micelles to reducing environments was investigated using the parameters of in vitro release and particle size. Intracellular release of nile red fluorescence alongside cytotoxicity studies further confirmed the potency of redox-sensitive micelles for intracellular drug delivery compared with redox-insensitive micelles. Additionally, an in vivo study confirmed the efficacy of PTX-loaded micelles in tumor-bearing mice with superior antitumor efficacy and diminished systemic toxicity when compared with the redox-insensitive micelles and a PTX solution. These results demonstrate the potential of redox-sensitive HECS-ss-OA micelles for intracellular trafficking of lipophilic anticancer drugs.
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