D-甘露糖修饰聚合物胶束的制备及其在靶向药物输送中的应用

D-mannose-conjugated polymeric micelles for targeted drug delivery

摘要:

聚合物胶束作为药物载体具有良好的稳定性和生物相容性，提高疏水性药物溶解性等优势，是一类很有应用潜力的药物传输系统。本研究以合成的共价键连D-甘露糖的双亲性聚合物分子 (PGMA-Mannose) 为药物载体，包载抗癌药物阿霉素 (DOX) 制备具有甘露糖受体靶向性和pH敏感药物释放特性的新型载药聚合物胶束。利用激光共聚焦显微镜和MTT细胞毒性评价方法对载药胶束的细胞内吞摄取和毒性进行评价。实验结果表明，载药胶束能特异性识别人乳腺癌细胞MDA-MB-231表面过度表达的甘露糖受体，被癌细胞大量摄取并在细胞溶酶体酸性环境内释放药物，而载药胶束在表面甘露糖受体低表达的HEK293细胞中只有少量摄取。与原药DOX相比，该载药胶束对癌细胞的毒性显著提高，而对正常细胞的毒性较低。因此，该PGMA-Mannose聚合物胶束有望成为一种新型的靶向药物输送系统应用于癌症的治疗。

Abstract:

Polymeric micelles have exhibited attractive properties as drug carriers, such as high stability in vivo and good biocompatibility, and been successfully used to dissolve various drugs of poor aqueous solubilities. In this study, we developed a new type of polymeric micelles with mannose-mediated targeting and pH-responsive drug release properties for anticancer drug delivery. The polymeric micelles were prepared from an amphiphilic polymer, poly (glycidyl methacrylate)-g-mannose (PGMA-Mannose). An anticancer drug, doxorubicin (DOX), was encapsulated into the micelles during the micellization, and could be released rapidly under acidic condition. The specificity of cellular uptake of the micelles by two different cell lines was studied using confocal laser scanning microscopy and the MTT assay. DOX-loaded micelles were efficiently trapped by mannose-receptor-overexpressing cancer cells MDA-MB-231, whereas mannose- receptor-poor cells HEK293 showed much lower endocytosis towards the micelles under the same conditions. Thus, DOX-loaded micelles displayed higher cytotoxicity to MDA-MB-231 cancer cells as compared with free DOX. The present study demonstrates that PGMA-Mannose micelles are a promising targeted drug delivery system for cancer therapy.