【作者】 唐国涛； 朱赛杰； 洪鸣凰； 姜嫣嫣； 裴元英；

【Author】 TANG Guotao1,2,ZHU Sai-jie1,HONG Ming-huang1,JIANG Yan-yan1,PEI Yuanying1 (1Department of Pharmaceutics,School of Pharmacy,Fudan Univeristy,Shanghai 201203,China. 2Department of Pharmacy,School of pharmacy and Life Science,Nanhua Univeristy,421001,Hengyang,Hunan,China.)

【机构】 复旦大学药学院； 南华大学药学与生命科学院；

【摘要】 目的探讨Tf修饰的主动靶向纳米载药复合物进行肿瘤靶向治疗的可行性。方法以琥珀酸酐为连接分子,制备载CPT的PAMAM-PEG复合物,以Tf为靶向头基,修饰在PEG外侧端构建主动靶向的长循环的纳米载药系统进行体外释放、肿瘤细胞摄取、细胞毒性、诱导细胞凋亡、大鼠体内药动学、荷瘤小鼠组织分布和抗肿瘤活性等研究。结果 Tf修饰的主动靶向复合物在体外能提高肿瘤细胞的摄取,增强抗肿瘤活性,低浓度条件时增加药物诱导肿瘤细胞凋亡的作用。可以延长药物在大鼠体内的半衰期和平均滞留时间,增加药物在S180荷瘤小鼠肿瘤部位的蓄积,增强体内抗肿瘤效果。结论主动靶向和被动靶向相结合的转铁蛋白-PEG-PAMAM-CPT复合物能进一步提高药物的抗肿瘤活性。更多还原

【Abstract】 OBJECTIVE To explore the potential of transferrin modified PEGylated polyamidoamine dendrimers (PEG-PAMAM) as the carrier for tumor targeting of the anticancer drug camptothecin(CPT). METHODS succinic linkage was introduced between CPT and PEG-PAMAM to produce CPP conjugates and Transferrin modified at the external of PEG. The effects of Tf-PAMAM-PEG-CPT on the in vitro release, cytotoxicity, cellular uptake, apoptosis induction, pharmacokinetics in normal rats, tissue distribution in tumor-bearing mice and in vivo anti-tumor activity were evaluated. RESULTS Tf-PAMAM-PEG-CPT could enhance cytotoxicty in tumor cells, increase the cellular uptake of tumor cells in vitro and strong the effect on inducing apoptosis at relative low concentration. In vivo, Tf-PAMAM-PEG-CPT could prolong the half life and MRT of drug in normal rats, enhance accumulation of drug in tumor tissue in S180 bearing mice and increase the efficiency of antitumor. CONCLUSION Tf-PAMAM-PEG-CPT could further enhance the antitumor activity by intergrating active targeting with passive targeting.更多还原