Reduction-responsive cross-linked micelles based on PEGylated polypeptides prepared via click chemistry
Reduction-responsive cross-linked micelles based on PEGylated polypeptides prepared via click chemistry
复制标题
基于通过点击化学制备的聚乙二醇化多肽的还原响应交联胶束
DOI：
10.1039/c3py00364g
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发表时间：
2013-01-01
影响因子：
4.6
通讯作者：
Chen, Xuesi
中科院分区：
文献类型：
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作者：
Cheng, Yilong;He, Chaoliang;Chen, Xuesi
本研究旨在通过点击化学方法制备新型的基于聚乙二烯glycol)-block-poly(gamma-propargyl-L-glutamate)的还原响应型交联胶束(CMS)。用核磁共振氢谱、红外光谱、动态光散射(DLS)和透射电子显微镜(TEM)证实了CMS的成功构建。阿霉素(DOX)作为模型抗癌药物被负载到CMS中。负载DOX的CMS能在生理条件下保持药物，并在谷胱甘肽(GSH)存在下迅速释放有效载荷。激光共聚焦扫描显微镜(CLSM)和流式细胞仪检测表明，随着细胞内GSH水平的升高，负载DOX的CMS细胞内药物释放增加。体外四甲基偶氮唑盐比色实验表明，负载DOX的CMS具有良好的生物相容性，对GSH处理的HeLa细胞的增殖抑制作用高于未处理的细胞。由于其独特的响应性，生物相容的CMS在癌症治疗中显示出细胞内给药的前景。
This study aims to develop novel reduction-responsive cross-linked micelles (CMs) based on poly(ethylene glycol)-block-poly(gamma-propargyl-L-glutamate) (PEG-PPLG) by click chemistry. H-1 NMR spectroscopy, IR spectroscopy, dynamic light scattering (DLS) and transmission electron microscopy (TEM) were performed to confirm the successful construction of the CMs. Doxorubicin (DOX) was loaded into the CMs as a model anticancer drug. The DOX-loaded CMs could hold the drug under physiological conditions, and release the payload quickly in the presence of glutathione (GSH). Confocal laser scanning microscopy (CLSM) and flow cytometry measurements revealed that the intracellular drug release from the DOX-loaded CMs was increased in the HeLa cells with an enhanced intracellular GSH level. In vitro methyl thiazolyl tetrazolium (MTT) assays indicated that the CMs were biocompatible, and DOX-loaded CMs showed higher cellular proliferation inhibition towards GSH-pretreated HeLa cells than non-pretreated cells. Due to their unique responsiveness, the biocompatible CMs show promise for the intracellular delivery of chemotherapeutic drugs in cancer therapy.