Wang Shuting, Zhang Quan, Ye Zhou, Xiong Yongquan, Cui Chenyu, Yin Jian
Sheng Wu Gong Cheng Xue Bao. 2016 Jan;32(1):84-94.
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.
聚合物胶束作为药物载体表现出了吸引人的特性,如在体内具有高稳定性和良好的生物相容性,并已成功用于溶解各种水溶性差的药物。在本研究中,我们开发了一种新型的具有甘露糖介导靶向和pH响应药物释放特性的聚合物胶束用于抗癌药物递送。该聚合物胶束由两亲性聚合物聚(甲基丙烯酸缩水甘油酯)-g-甘露糖(PGMA-甘露糖)制备而成。一种抗癌药物阿霉素(DOX)在胶束形成过程中被包裹进胶束中,并且在酸性条件下能够快速释放。使用共聚焦激光扫描显微镜和MTT法研究了两种不同细胞系对胶束的细胞摄取特异性。负载DOX的胶束被甘露糖受体过表达的癌细胞MDA-MB-231有效捕获,而甘露糖受体含量低的细胞HEK293在相同条件下对胶束的内吞作用则低得多。因此,与游离DOX相比,负载DOX的胶束对MDA-MB-231癌细胞显示出更高的细胞毒性。本研究表明,PGMA-甘露糖胶束是一种有前途的用于癌症治疗的靶向药物递送系统。