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目的:利用聚合物纳米胶束靶向输送光敏剂分子已经成为光动力治疗癌症的研究热点。方法:采用原子转移自由基聚合反应合成嵌段聚合物聚丙烯酸叔丁酯-聚甲基丙烯酸缩水甘油酯(Pt BA-b-PGMA),共聚物的一端脱除叔丁基,通过缩合反应共价键连接甘露糖分子,另一端环氧基开环引入叠氮基,并通过“click”反应共价连接氟硼二吡咯光敏剂分子,最后制备得到表面甘露糖修饰的负载光敏剂聚合物胶束。利用核磁共振氢谱仪和傅立叶变换红外光谱仪进行结构确认;通过透射电镜和动态光散射等考察其理化性质;经激光共聚焦显微镜和MTT细胞毒性实验对其甘露糖受体靶向性及光动力疗效进行考察和评价。结果:聚合物Pt BA-b-PGMA的相对分子量为16 924,其分散系数为1.36。聚合物中环氧基开环引入叠氮后在2 106 cm-1处出现叠氮基特征峰。经过“click”反应引入氟硼二吡咯光敏剂分子后,叠氮基特征峰消失,在1 637 cm-1处出现三氮唑特征峰。聚合物胶束粒径分布均一,稳定性良好。胶束平均流体力学直径为178 nm,在水溶液中粒度分布较窄(PDI=0.298)。聚合物胶束对人乳腺癌MDA-MB-231细胞和HEK293正常细胞均无暗毒性,在535 nm LED光照下对乳腺癌MDA-MB-231细胞具有较好的光动力治疗效果。结论:聚合物胶束能被MDA-MB-231癌细胞表面高表达的甘露糖受体特异性识别,并被内吞进入癌细胞内,具有较好的光动力杀伤作用。
OBJECTIVE: Targeted delivery of photosensitizer molecules by polymer nanomicelles has become a research focus of photodynamic therapy for cancer. Methods: The block copolymer poly (t-butyl acrylate) -polyglycidyl methacrylate (Pt BA-b-PGMA) was synthesized by atom transfer radical polymerization. One end of the copolymer was removed t- The valence bond is connected to the mannose molecule, the other end of the epoxy group is ring-opened to introduce the azide group, and the fluoroborodipyr photosensitizer molecule is covalently linked through the “click” reaction. Finally, the surface mannose-modified supported photosensitizer is polymerized Micelles. The structures were confirmed by 1H nuclear magnetic resonance spectroscopy and Fourier transform infrared spectroscopy. The physical and chemical properties were examined by transmission electron microscopy and dynamic light scattering. The targeting and photodynamic activities of mannose receptor by laser confocal microscopy and MTT cytotoxicity The efficacy of inspection and evaluation. Results: The relative molecular weight of polymer Pt BA-b-PGMA was 16 924 with a dispersion coefficient of 1.36. In the polymer, ring opening of the polymer led to azide characteristic peak at 2 106 cm-1 after introducing azide. After the “click” reaction introduced fluorine boron dipyrromethene photosensitizer molecule, the azide characteristic peak disappeared, and the characteristic peak of triazole appeared at 1 637 cm-1. Polymer micelle particle size distribution is uniform, good stability. The average hydrodynamic diameter of the micelles was 178 nm, with a narrow particle size distribution (PDI = 0.298) in aqueous solution. Polymeric micelles showed no toxicity to human breast cancer MDA-MB-231 cells and normal HEK293 cells, and had good photodynamic therapy effect on breast cancer MDA-MB-231 cells under the light of 535 nm LED. CONCLUSION: Polymer micelles can be specifically recognized by mannose receptor highly expressed on the surface of MDA-MB-231 cancer cells and endocytosed into cancer cells with good photodynamic killing effect.