College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, China; National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, China.
Biomaterials. 2014 May;35(15):4517-24. doi: 10.1016/j.biomaterials.2014.01.067. Epub 2014 Mar 5.
Four arm star-shaped poly(ε-caprolactone)-b-poly((N,N-diethylaminoethyl methacrylate)-r-(N-(3-sulfopropyl)-N-methacryloxyethy-N,N-diethylammoniumbetaine)) (4sPCLDEAS) micelles were loaded with anticancer drug doxorubicin to track their endocytosis in Hela cancer cell line. The effects of mean diameters and surface charges of the drug loaded micelles on the cellular uptake were studied in details. The results demonstrated that the internalization of micelles was both time and energy dependent process. Endocytic pathways including clathrin-mediated endocytosis, caveolae-mediated endocytosis and macropinocytosis were all involved in the internalization; caveolae-mediated endocytosis was the main pathway for the internalization of 4sPCLDEAS micelles. The assays for cell apoptosis and growth inhibition of tumor spheroids identified that these doxorubicin loaded micelles could induce cell apoptosis and inhibit tumor spheroids growth efficiently, which was even equal to free DOX·HCl. This study provided a rational design strategy for fabricating diverse micellar drug delivery systems with high anticancer efficiency.
四臂星形聚（ε-己内酯）-b-聚（（N，N-二乙基氨基乙基甲基丙烯酸酯）-r-（N-（3-磺丙基）-N-甲基丙烯酰氧基乙基-N，N-二乙基铵甜菜碱））（4sPCLDEAS）胶束被加载抗癌药物阿霉素，以跟踪其在 Hela 癌细胞系中的内吞作用。详细研究了载药胶束的平均直径和表面电荷对细胞摄取的影响。结果表明，胶束的内化是一个时间和能量依赖的过程。包括网格蛋白介导的内吞作用、小窝介导的内吞作用和巨胞饮作用在内的内吞作用途径都参与其中；小窝介导的内吞作用是 4sPCLDEAS 胶束内化的主要途径。细胞凋亡和肿瘤球体生长抑制的测定表明，这些载阿霉素的胶束能够有效诱导细胞凋亡并抑制肿瘤球体的生长，其效果甚至与游离 DOX·HCl 相当。该研究为制备具有高效抗癌作用的多种胶束药物递送系统提供了合理的设计策略。
