School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, PR China.
School of Bioscience & Bioengineering, South China University of Technology, Guangzhou 510640, PR China.
Mater Sci Eng C Mater Biol Appl. 2018 Jan 1;82:1-9. doi: 10.1016/j.msec.2017.08.026. Epub 2017 Aug 10.
Increasing target to tumor sites and reducing accumulation at normal tissue sites of anticancer drugs are essential to improve the cancer chemotherapy efficiency. In this study, we have developed a novel pentablock polymeric poly(ethylene glycol)-b-(poly(2-(diethylamino) ethyl methacrylate)-b-poly (hydroxyethyl methacrylate)-g-folic acid) [PEG-b-(PDEAEMA-b-PHEMA-g-FA)] micelles as anticancer drug nanocarrier. The carriers could target tumor cells rapidly, and response to the tumor sites pH to control drug release. The critical micelle concentration (CMC) of the intermediates copolymers was 4.37-7.08mg/L, which indicated that the self-assembled micelles had comparatively good internal circulation stability. The drug loaded micelles were prepared using dialysis method, resulting in an average particle size of below 120nm, and the drug loading content and entrapment efficiency were 21% and 48% respectively. The pH-responsiveness and in vitro drug release of the micelles were studied, and the results showed a higher doxorubicin (DOX) cumulative amount at pH5.0 (90%) compared to pH7.4 (20%) owing to the protonation of the tertiary amino groups. In vitro cytotoxicity and endocytosis experiments showed that the tumor-suppressing effect of drug-loaded micelles was close to those of free DOX. The loaded DOX could be delivered into the cancer cells in a short time, and about 80% of the tumor cells were killed after 48h incubation. The results indicate that the pentablock polymeric micelles have the potential to be applied for targeting anticancer drug delivery and control release.
提高抗癌药物在肿瘤部位的靶向性，减少在正常组织部位的积累，对于提高癌症化疗效率至关重要。在这项研究中，我们开发了一种新型的五嵌段聚合物聚乙二醇-b-（聚（2-（二乙氨基）乙基甲基丙烯酸酯）-b-聚（羟乙基甲基丙烯酸酯）-g-叶酸）[PEG-b-（PDEAEMA-b-PHEMA-g-FA）]胶束作为抗癌药物纳米载体。该载体能够快速靶向肿瘤细胞，并响应肿瘤部位的 pH 值来控制药物释放。中间体共聚物的临界胶束浓度（CMC）为 4.37-7.08mg/L，表明自组装胶束具有较好的内部循环稳定性。采用透析法制备载药胶束，平均粒径小于 120nm，载药量和包封率分别为 21%和 48%。研究了载药胶束的 pH 响应性和体外药物释放，结果表明，在 pH5.0 时（90%），由于叔氨基质子化，阿霉素（DOX）的累积量明显高于 pH7.4 时（20%）。体外细胞毒性和内吞实验表明，载药胶束的抑瘤效果与游离 DOX 相近。载药 DOX 可以在短时间内递送到癌细胞中，孵育 48h 后约 80%的肿瘤细胞被杀死。结果表明，五嵌段聚合物胶束具有作为靶向抗癌药物递送和控制释放的潜力。
