【摘要】 介绍了制备一种γ-聚谷氨酸-D-半乳糖酯化衍生物-顺铂复合物[poly(γ-glutamic acid)-D-galactose esterifiable derivative-cisplatin complex compound,γ-D+-DDP],并考察其抗肿瘤活性。主要通过生物发酵获得大分子γ-聚谷氨酸[poly(γ-glutamic acid),γ-PGA],利用酸降解得到可以作为药物载体的小分子γ-聚谷氨酸;利用凝胶色谱柱检验小分子γ-聚谷氨酸的分子量;利用MTT法检测该复合物的体外抗肿瘤作用。结果表明:成功获得γ-聚谷氨酸-D-半乳糖酯化衍生物-顺铂复合物,该复合物载药率达9.4%~10.2%;该复合物对人肝癌细胞BEL-7402具有显著的杀伤作用,能引起细胞凋亡(HE染色观察得到)。因此,γ-聚谷氨酸-D-半乳糖酯化衍生物-顺铂复合物是一种有效的抗肿瘤药物,具有潜在的临床应用价值;生物发酵的γ-聚谷氨酸可用于药物载体,赋予药物新的特点。更多还原

【Abstract】 The study was to develop cis-dichlorodiammineplatinum(DDP)-loaded formulations using a novel type of self-assembled compound composed of block copolymers synthesized by poly(γ-glutamic acid)(γ-PGA).For the potential of targeting liver cancer cells,D-galactose was conjugated on the prepared γ-PGA.In vitro,DDP can be released from the resulting conjugate in PBS:there was a burst release during the first 8 h,then followed by sustained release.DDP could be easily incorporated into poly(γ-glutamic acid)-D-galactose esterifiable derivative through a covalent bond.The yield of DDP incorporation into the esterifiable derivative was 9.4%～10.2%.In vitro experiments conclusively established that the poly(γ-glutamic acid)-D-galactose esterifiable derivative-Cisplatin Complex Compound(γ-D+-DDP)was much less toxic to normal cell lines than DDP only.The surviving rate of cells treated with γ-D+-DDP compound is higher than those treated with free DDP.Also it has obvious antitumor efficiency on human liver tumor BEL-7402 cells.HE staining indicated that the γ-D+-DDP compound make the BEL-7402 apoptosis.These results indicated that the conjugation of DDP to the esterifiable derivative reduced its cytotoxicity activity,but retains its antitumor activity in vitro.In conclusion,the γ-D+-DDP compound could be used as a potential clinic antitumor drug.The γ-PGA obtained by fermentation can be used as a valuable drug carrier system.更多还原