包裹外毒素Ⅲ的VEGF-脂质体靶向杀伤肿瘤血管内皮细胞的实验研究  

VEGF-liposomes Encapsulating Domain Ⅲ of Pseudomonas Exotoxin in the Targeting of Human Tumor-derived Vascular End othelial Cells in vitro

作　　者：童强[1] 王国斌[1] 卢晓明[1] 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普外科,武汉430022

出　　处：《华中科技大学学报（医学版）》2004年第6期700-703,共4页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家高技术研究发展计划 (86 3计划 )资助项目 (No.2 0 0 1AA2 180 5 1)

摘　　要：目的　利用包裹绿脓杆菌外毒素单元Ⅲ的VEGF (血管内皮生长因子 ) 脂质体于体外靶向杀伤肿瘤血管内皮细胞。方法　通过结合实验 ,验证VEGF连接脂质体对肿瘤血管内皮细胞具有特异结合能力。利用体外细胞毒实验(MTT)方法 ,检测外毒素单元Ⅲ及靶向脂质体包裹的单元Ⅲ对肿瘤血管内皮细胞的杀伤作用。结果　连有VEGF的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性结合 ,结合率可达非特异性脂质体的 2倍。在去除外毒素单元Ⅰ和Ⅱ后 ,单元Ⅲ的细胞毒作用消失 ,但包裹单元Ⅲ的VEGF 脂质体可特异性杀伤肿瘤血管内皮细胞。结论　VEGF 脂质体可特异性地识别肿瘤血管内皮细胞 ,并作为良好载体将绿脓杆菌外毒素单元Ⅲ带入细胞 ,实现其杀伤作用 ,可望成为一种有效的抗肿瘤物质。Objective To evaluate the targeting ability and cytotoxicity of domain Ⅲ of pseudomonas exotoxin encapsulated in liposomes conjugated with VEG F in vitro. Methods Binding ability of liposomes conjugated with VEGF to tu mor-derived vascular endothelial cells was detected by binding assay. MTT assay was used to detect the cytotoxicity of free domain Ⅲand domain Ⅲencapsulated in VEGF-liposomes against tumor-derived vascular endothelial cells. Results At least 2-fold increase in binding for the targeted l iposomes was observed. Liposomes conjugated with VEGF could highly selectively b ound to VEGFR expressing endothelial cells. The cytotoxicity of free domain Ⅲ d isappeared when domain I and domain Ⅱ were deleted. But when domain Ⅲ was enca psulated into VEGF-liposomes, the cytotoxicity against tumor-derived vascular endothelial cells was significantly increased. Conclusion Lipos omes conjugated with VEGF, as drug carriers, can specifically recognize tumor-d erived vascular endothelial cells and deliver domain Ⅲof pseudomonas exotoxin i nto the cells. This formulation of domain Ⅲ-liposomes conjugated with VEGF mig ht be an effective anti-tumor agent.

关 键 词：肿瘤血管 内皮细胞 脂质体 VEGF 靶向 绿脓杆菌外毒素 杀伤作用 特异性结合 消失 载体 

分 类 号：R730[医药卫生—肿瘤] R735[医药卫生—临床医学]