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
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R943

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

    Abstract:

    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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汪家伟,张权,叶舟,崔晨宇,尹健.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[J].食品与生物技术学报,2019,38(2):50-58.

WANG Jiawei, ZHANG Quan, YE Zhou, CUI Chenyu, YIN Jian. Mannose-Conjugated Polymeric Micelles with Different Sizes for Targeted Drug Delivery[J]. Journal of Food Science and Biotechnology,2019,38(2):50-58.

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  • 在线发布日期: 2019-03-28
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