不同粒径大小的甘露糖修饰聚合物胶束制备及其靶向药物输送应用

Mannose-Conjugated Polymeric Micelles with Different Sizes for Targeted Drug Delivery

DOI：10.3969/j.issn.1673-1689.2019.02.008

中文关键词: D-甘露糖 聚合物胶束 靶向药物输送 细胞内吞 细胞毒性

英文关键词: D-mannose,polymeric micelles,targeted drug delivery,endocytosis,cytotoxicity

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中文摘要:

采用原子转移自由基聚合（ATRP）反应合成不同嵌段比例的嵌段聚合物聚甲基丙烯酸丙酮缩甘油酯-聚甲基丙烯酸缩水甘油酯（PSA-b-PGMA），并通过"click"反应在聚合物上进行D-甘露糖修饰，得到了甘露糖修饰的两亲性聚合物聚甲基丙烯酸丙酮缩甘油酯-聚甲基丙烯酸缩水甘油酯-甘露糖（PSA-b-PGMA-Mannose）。利用该两亲性聚合物在水中自组装形成胶束，并通过胶束的疏水空腔包裹抗癌药物阿霉素（DOX）。PSA-b-PGMA-Mannose的分子结构通过核磁共振氢谱和傅立叶变换红外光谱表征确认。所形成胶束的形貌和粒径通过透射电镜和动态光散射进行表征。载药胶束的细胞内吞摄取以及细胞毒性通过激光共聚焦显微镜和MTT细胞毒性方法进行评价。实验结果表明：不同嵌段比的两亲性聚合物所形成的胶束，随着聚合物中亲水性链段的比例增大，形成胶束的粒径逐渐减小。同时，甘露糖受体过度表达的人乳腺癌细胞MDA-MB-231能够特异性识别并大量摄取载药胶束，从而在癌细胞内释放药物DOX发挥药效。

英文摘要:

The poly（solketal methacrylate）-block-poly（glycidyl methacrylate）（PSA-b-PGMA） copolymer is synthesized by atom transfer radical polymerization（ATRP） and functionalized with mannose by the "click" reaction to yield PSA-b-PGMA-Mannose. These copolymers are used to prepare polymeric micelles，and an anticancer drug，doxorubicin（DOX），is encapsulated into the micelles by oil-water method. Structure of PSA-b-PGMA-Mannose is confirmed by 1H NMR and FT-IR. The size and morphologie of PSA-b-PGMA-Mannose with different block ratios were characterized by transmission electron microscopy and dynamic light scattering. The in vitro cytotoxicity and cellular uptake against MDA-MB-231 cancer cells were evaluated by confocal laser scanning microscopy and MTT assay. The results show a decrease in the average size of micelles upon an increase in the hydrophilic/hydrophobic block ratio. The DOX-loaded micelles are efficiently trapped by MDA-MB-231 cancer cells via receptor-mediated endocytosis and releass loaded DOX into the cells.

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