阿霉素
前药
谷胱甘肽
羟乙基淀粉
药理学
细胞毒性
体内
细胞内
结合
药物输送
细胞外
体外
化疗
化学
医学
材料科学
生物化学
生物
纳米技术
内科学
酶
生物技术
数学分析
数学
作者
Hang Hu,Yihui Li,Qing Zhou,Yanxiao Ao,Chang Yu,Ying Wan,Huibi Xu,Zifu Li,Xiangliang Yang
标识
DOI:10.1021/acsami.6b11932
摘要
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 (∼2 μM) 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.
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