期刊
ACS APPLIED MATERIALS & INTERFACES
卷 8, 期 45, 页码 30833-30844出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.6b11932
关键词
redox-sensitive; conjugate; hydroxyethyl starch; doxorubicin; tumor targeted drug delivery; chemotherapy
资金
- National Basic Research Program of China (program 973) [2012CB932500]
- National Science Foundation of China [81201193, 81372400, 81473171, 51103051]
Doxorubicin (DOX) is one of the most potent anticancer agents in cancer chemotherapy, but the clinical use of DOX is restricted by its severe side effects caused by nonspecific delivery. To alleviate the side effects and improve the antitumor efficacy of DOX, a novel redox-sensitive hydroxyethyl starch doxorubicin conjugate, HES-SS-DOX, with diameter of 19.9 +/- 0.4 nm was successfully prepared for tumor targeted drug delivery and GSH-mediated intracellular drug release. HES-SS-DOX was relatively stable under extracellular GSH level (similar to 2 mu M) but released DOX quickly under intracellular GSH level (2-10 mM). In vitro cell study confirmed the GSH-mediated cytotoxicity of HES-SS-DOX. HES-SS-DOX exhibited prolonged plasma half-life time and enhanced tumor accumulation in comparison to free DOX. As a consequence, HES-SS-DOX exhibited better antitumor efficacy and reduced toxicity as compared to free DOX in the in vivo antitumor activity study. The redox-sensitive HES-SS-DOX was proved to be a promising prodrug of DOX, with clinical potentials, to achieve tumor targeted drug delivery and timely intracellular drug release for effective and safe cancer chemotherapy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据