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Redox-responsive dasatinib-containing hyaluronic acid prodrug and co-delivery of doxorubicin for cancer therapy
International Journal of Polymeric Materials and Polymeric Biomaterials ( IF 2.5 ) Pub Date : 2020-07-29 , DOI: 10.1080/00914037.2020.1798434
Yin-Ku Lin, Shiu-Wei Wang, Ren-Shen Lee

Abstract

Redox-responsive prodrugs were synthesized by conjugating dasatinib (Das)/cholesterol (Chol) to hyaluronic acid (HA) via the cystamine dihydrochloride (Cys), and hexamethylene diamine (Hda) linkers. In a redox environment (10 mM dithiothreitol, DTT), a substantial amount of the grafted Das was released and faster than that observed under physiological conditions. The cytotoxicity of redox-sensitive HA-Cys-P(SSDas/CCChol) was greater than that of redox-insensitive HA-Hda-PCCDas. Flow cytometry showed that the uptake of HA-targeted DOX–encapsulated micelles was faster than that of free DOX.



中文翻译:

氧化还原反应性达沙替尼的透明质酸前药和阿霉素的共同递送用于癌症治疗

摘要

通过将达沙替尼 (Das)/胆固醇 (Chol) 通过胱胺二盐酸盐 (Cys) 和六亚甲基二胺 (Hda) 接头与透明质酸 (HA) 结合来合成氧化还原反应性前药。在氧化还原环境(10 mM 二硫苏糖醇,DTT)中,大量接枝的 Das 被释放,并且比在生理条件下观察到的更快。氧化还原敏感的HA-Cys-P(SSDas/CCChol)的细胞毒性大于氧化还原不敏感的HA-Hda-PCCDas。流式细胞术显示,HA 靶向 DOX 包裹的胶束的吸收比游离 DOX 快。

更新日期:2020-07-29
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