胶束
活性氧
化学
药物输送
胞浆
药品
氧气
癌症
生物物理学
生物化学
药理学
酶
有机化学
生物
水溶液
遗传学
作者
Yu Lu,Geng Min Su,Chi Kang Chen,Yi-Pin Chiang,Chun Liang Lo
出处
期刊:Biomacromolecules
[American Chemical Society]
日期:2016-08-26
卷期号:17 (9): 3040-3047
被引量:33
标识
DOI:10.1021/acs.biomac.6b00916
摘要
Cytosolic drug delivery, a major route in cancer therapy, is limited by the lack of efficient and safe endosomal escape techniques. Herein, we demonstrate a reactive oxygen species (ROS)-responsive micelle composed of methoxy polyethylene glycol-b-poly(diethyl sulfide) (mPEG-PS) copolymers which can induce specific endosome escape in cancer cells by changes in the hydrophobicity of copolymers. Owing to the more ROS levels in cancer cells than normal cells, the copolymers can be converted into more hydrophilic and insert into and destabilize the cancer intracellular endosome membrane after cellular uptake. More importantly, we show that acid-intolerant drugs successfully maintain their bioactivity and cause selective cytotoxicity for cancer cells over normal cells. Our results suggest that the endosomal escape induced by hydrophobic-hydrophilic exchange of copolymers has great potential to locally and efficiently deliver biological agents (e.g., proteins and genes) in the cancer cell cytosol.
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