血管内皮生长因子-阿霉素脂质体的制备及体外靶向杀伤肿瘤血管内皮细胞的研究  

Preparation of adriamycin liposomes conjugated with VEGF and its targeting action on human tumor-derived vascular endothelial cells in vitro

作　　者：童强[1] 王国斌[1] 卢晓明[1] 宋波[2] 黎维勇[2] 陶凯雄[3] 陈道达[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院胃肠外科,武汉430022 [2]华中科技大学同济医学院附属协和医院药剂科,武汉430022 [3]华中科技大学同济医学院附属协和医院腔镜外科,武汉430022

出　　处：《中华实验外科杂志》2005年第3期313-315,i008,共4页Chinese Journal of Experimental Surgery

基　　金：国家高技术研究"十五"发展计划(863计划)基金资助项目(2001AA218051)

摘　　要：目的利用包裹阿霉素的血管内皮生长因子(VEGF)脂质体于体外靶向杀伤肿瘤血管内皮细胞。方法利用体外细胞毒实验四甲基偶氮唑蓝比色法(MTT),检测VEGF阿霉素脂质体对肿瘤血管内皮细胞的杀伤作用。结果连有VEGF的阿霉素脂质体可与表达血管内皮生长因子受体(VEGFR)的肿瘤血管内皮细胞特异结合,结合率可达非特异性脂质体的2倍。载药的VEGF脂质体可特异杀伤肿瘤血管内皮细胞。48h细胞毒试验连有VEGF的阿霉素脂质体对肿瘤血管内皮细胞的杀伤作用优于无VEGF的阿霉素脂质体(P<0.05),而对非靶细胞(人血管平滑肌细胞)的杀伤作用两者相近。0.5h预处理试验表明缩短药物与细胞接触时间后,VEGF阿霉素脂质体仍保持较强的杀伤肿瘤血管内皮细胞的作用。结论VEGF脂质体可特异性的识别肿瘤血管内皮细胞,并作为良好载体将阿霉素带入细胞,实现其杀伤作用。ObjectiveTo evaluate the targeting ability and cytotoxicity of adriamycin liposomes conjugated with VEGF in vitro.Methods MTT assay was used to detect the cytotoxicity of adriamycin liposomes conjugated with VEGF against tumor-derived vascular endothelial cells.Results Adriamycin liposomes conjugated with VEGF could be highly selectively bond to endothelial cells expressing VEGFR with at least 2-fold increase in binding for the targeted liposomes.Moreover,the cytotoxicity produced by adriamycin liposomes conjugated with VEGF was greatly enhanced as compared with that by non-targeted liposomes.48-h cytotoxicity assay with MTT method revealed that specific cytotoxicity of VEGF-liposomes to endothelial cells were 28.6 fold more effective than the control non-VEGF-liposomes group,but with very similar cytotoxicity to non-targeted smooth muscle cells.0.5 h pretreatment assay demonstrated that cytotoxicity of free ADM on endothelial cells was decreased remarkably (IC50=76.7 μmol/L),but adriamycin liposomes conjugated with VEGF remained higher activity (IC50=6.12 μmol/L) than control non-VEGF-liposomes group (IC50>100 μmol/L) after reducing the contact time (to 0.5 h) between drugs and cells.Conclusion Liposomes conjugated with VEGF,as drug carriers,can specifically recognize tumor-derived vascular endothelial cells and deliver adriamycin into the cells.

关 键 词：肿瘤血管 脂质体 内皮细胞 阿霉素 VEGF 杀伤作用 体外 靶细胞 特异性 载体 

分 类 号：R73-3[医药卫生—肿瘤]