Dual-stimuli sensitive keratin graft PHPMA as physiological trigger responsive drug carriers
Dual-stimuli sensitive keratin graft PHPMA as physiological trigger responsive drug carriers
复制标题
双刺激敏感角蛋白移植物 PHPMA 作为生理触发响应药物载体
DOI：
10.1039/c4py01750a
复制
发表时间：
2015-01-01
影响因子：
4.6
通讯作者：
Huang, Yong
中科院分区：
文献类型：
--
作者：
Li, Qinmei;Yang, Saina;Huang, Yong
合成并表征了角蛋白接枝聚（N-（2-羟丙基）甲基丙烯酰胺）（K-g-PHPMA）共聚物。考虑到角蛋白的巯基和接枝共聚物的两亲性，在水中制备了角蛋白核上具有可裂解交联的胶束。K-g-PHPMA胶束能有效地包封阿霉素（DOX），可作为药物载体。胶束中的DOX含量随着接枝共聚物中角蛋白含量的增加而增加。胶束中包封的DOX的释放对生理环境敏感。氧化还原触发谷胱甘肽（GSH），特别是在细胞内水平，并且胰蛋白酶可以有效地触发包封的DOX的释放。体外细胞摄取实验表明，从DOX负载的K-g-PHPMA胶束释放的DOX可以有效地内化到细胞中。在较高GSH条件下，DOX显示更快地释放到细胞核中。K-g-PHPMA共聚物作为药物载体在肿瘤治疗中具有良好的应用前景。
Keratin graft poly(N-(2-hydroxypropyl)methacrylamide) (K-g-PHPMA) copolymers were synthesized and characterized. On account of the thiol groups of keratin and the amphiphilicity of the graft copolymers, micelles with cleavable cross-links on a keratin core were fabricated in water. The K-g-PHPMA micelles can efficiently encapsulate doxorubicin (DOX) and can be used as a drug carrier. The DOX content in the micelles increases with the keratin content of the graft copolymers. The release of the encapsulated DOX in the micelles is sensitive to the physiological environment. Redox trigger glutathione (GSH), especially at the intracellular level, and trypsin can effectively trigger the release of the encapsulated DOX. In vitro cellular uptake experiments indicate that the DOX released from the DOX-loaded K-g-PHPMA micelles can be efficiently internalized into cells. Under higher GSH condition, the DOX shows a much faster release into the nucleus of the cells. The K-g-PHPMA copolymers have promising applications as drug carriers for enhanced intracellular drug delivery in cancer therapy.