Biodegradable micelles with sheddable poly(ethylene glycol) shells for triggered intracellular release of doxorubicin
Biodegradable micelles with sheddable poly(ethylene glycol) shells for triggered intracellular release of doxorubicin
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具有可脱落聚乙二醇壳的可生物降解胶束，用于触发阿霉素的细胞内释放
DOI：
10.1016/j.biomaterials.2009.07.051
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发表时间：
2009-11-01
期刊：
影响因子：
14
通讯作者：
Zhong, Zhiyuan
中科院分区：
文献类型：
--
作者：
Sun, Huanli;Guo, Bingnan;Zhong, Zhiyuan
以二硫化物-聚乙二醇-b-聚己内酯（PEG-SS-PCL）二嵌段共聚物为基础，制备了具有可脱落聚乙二醇壳的可生物降解胶束，并应用于多柔比星（DOX）的细胞内快速释放。PEG- ss -PCL通过PEG正吡啶二硫化物和巯基PCL的交换反应制备了具有控制嵌段长度的PEG- ss -PCL。PEG- ss -PCL形成的胶束虽然在水中足够稳定，但在10 mm二硫苏糖醇（DTT）存在下容易快速聚集，这是由于PEG壳通过中间二硫键的还原裂解而脱落。有趣的是，体外释放研究表明，这些可脱壳胶束在类似于胞浆和细胞核等胞内区室的还原环境下，在12小时内定量释放DOX。相比之下，最小的药物释放(
Biodegradable micelles with sheddable poly(ethylene glycol) shells were developed based on disulfide-linked poly(ethylene glycol)-b-poly(epsilon-caprolactone) (PEG-SS-PCL) diblock copolymer and applied for rapid intracellular release of doxorubicin (DOX). PEG-SS-PCL was prepared with controlled block lengths via exchange reaction between PEG orthopyridyl disulfide and mercapto PCL The micelles formed from PEG-SS-PCL, though sufficiently stable in water, were prone to fast aggregation in the presence of 10 mm dithiothreitol (DTT), due to shedding of the PEG shells through reductive cleavage of the intermediate disulfide bonds. Interestingly, the in vitro release studies revealed that these shell-sheddable micelles released DOX quantitatively within 12 h under a reductive environment analogous to that of the intracellular compartments such as cytosol and the cell nucleus. In contrast, minimal drug release (