RGD肽修饰的聚谷氨酸-顺铂复合物的体外评价

In vitro evaluation of RGD peptide-modified polyglutamic acid-cisplatin conjugate

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。

Objective： To prepare RGD peptide-modified polymer-drug conjugate using polyglutamic acid as cisplatin targeted delivery system and evaluate its physicochemical properties,in vitro cytotoxicity and celluar uptake. Methods： The polymer-drug conjugate synthesized by coordination reaction of cisplatin and polygultamic acid was coupled with RGDf K to obtain RGD peptide-modified polymer-drug conjugate. The drug loading,in vitro release,cytotoxicity and cellular uptake rate were determined. Results： The drug loading rates of the conjugates were23. 12% and 16. 73% for non-modified and RGD peptide-modified conjugates,respectively. The two types of conjugates showed no obvious difference in in vitro sustained-release of cisplatin. Compared to non-modified conjugate,the RGD peptide-modified conjugate was uptaken by MDA-MB-231 and MCF-7 to a greater extent. Conclusion：The RGD peptide-modified conjugates might be a potential formulation for targeting cancer therapy in patients.