RGD肽修饰的聚谷氨酸-顺铂复合物的体外评价

发布时间：2019-02-16 08:21

【摘要】：目的:本研究以经柠檬酸改性的聚谷氨酸为载体,制备聚谷氨酸-顺铂复合物,接枝环RGD肽,以提高该复合物对肿瘤细胞的靶向性,同时对所得到的高分子-药物复合物体外理化性质和细胞毒作用、细胞摄取进行评价。方法:以改性聚谷氨酸侧链羧基与顺铂稳定配位,再与RGD肽进行化学偶联,得到修饰后的药物复合物,对复合物的载药量等性质进行了考察,同时采用人乳腺癌MDA-MB-231细胞和MCF-7细胞进行了体外细胞生长抑制和细胞摄取行为的评价。结果:与未修饰的聚合物-药物复合物(23.12%)比较,本研究所制备主动靶向聚谷氨酸-顺铂复合物的载药量略有下降(16.73%),体外释放参数无显著差异,表现出明显的缓释特征。体外细胞毒实验结果表明,两类复合物保留了顺铂对肿瘤细胞的毒性,相比无RGD修饰的复合物,人乳腺癌MDA-MB-231和MCF-7细胞对RGD修饰的复合物摄取增强。结论:RGD修饰的顺铂-聚谷氨酸复合物成功制备,有利于提高针对体内肿瘤的缓释、靶向治疗效果。
[Abstract]:Aim: to prepare polyglutamic acid-cisplatin complex with citric acid modified polyglutamic acid as carrier and graft cyclic RGD peptide to improve its targeting to tumor cells. At the same time, the physicochemical properties, cytotoxicity and cellular uptake of the polymer-drug complexes in vitro were evaluated. Methods: the modified poly (glutamic acid) side chain carboxyl group was stably coordinated with cisplatin, then chemically coupled with RGD peptide to obtain the modified drug complex. Human breast cancer MDA-MB-231 cells and MCF-7 cells were used to evaluate cell growth inhibition and cell uptake in vitro. Results: compared with unmodified polymer-drug complexes (23.12%), the amount of active target polyglutamic acid-cisplatin complexes was slightly decreased (16.73%), and there was no significant difference in vitro release parameters. It shows obvious slow release characteristics. The results of cytotoxicity test in vitro showed that the two kinds of complexes retained the toxicity of cisplatin to tumor cells. Compared with the complexes without RGD modification, the uptake of RGD modified complexes by MDA-MB-231 and MCF-7 cells of human breast cancer increased. Conclusion: the successful preparation of RGD modified cisplatin-polyglutamic acid complex is beneficial to improve the sustained release and target therapeutic effect of tumor in vivo.
【作者单位】：中国药科大学药学院;
【基金】：中央高校基本科研业务费科研专项基金(ZJ14141)
【分类号】：R943;R96

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