National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology , Wuhan 430074, People's Republic of China.
Wuhan Institute of Biotechnology , High Tech Road 666, East Lake High Tech Zone, Wuhan 430040, People's Republic of China.
ACS Appl Mater Interfaces. 2016 Nov 16;8(45):30833-30844. doi: 10.1021/acsami.6b11932. Epub 2016 Nov 7.
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.
多柔比星（DOX）是癌症化疗中最有效的抗癌药物之一，但由于其非特异性递送，其临床应用受到限制。为了减轻 DOX 的副作用并提高其抗肿瘤疗效，我们成功制备了一种新型的氧化还原敏感的羟乙基淀粉-多柔比星偶联物 HES-SS-DOX，其直径为 19.9±0.4nm，可用于肿瘤靶向药物递送和 GSH 介导的细胞内药物释放。在细胞外 GSH 水平（约 2μM）下，HES-SS-DOX 相对稳定，但在细胞内 GSH 水平（2-10mM）下迅速释放 DOX。体外细胞研究证实了 HES-SS-DOX 的 GSH 介导的细胞毒性。与游离 DOX 相比，HES-SS-DOX 表现出更长的血浆半衰期和增强的肿瘤积累。因此，在体内抗肿瘤活性研究中，与游离 DOX 相比，HES-SS-DOX 表现出更好的抗肿瘤疗效和更低的毒性。氧化还原敏感的 HES-SS-DOX 被证明是一种有前途的 DOX 前药，具有临床潜力，可实现肿瘤靶向药物递送和及时的细胞内药物释放，以实现有效和安全的癌症化疗。
Zotero 插件