靶向肝癌细胞高分子造影剂的制备及其体外寻靶实验  

Preparation and in vitro study of a high molecular weight contrast agent targeting hepatoma cells

作　　者：杨静[1] 曾燕[1] 郭大静[1] 方正[1] 赵建农[1] 王志刚[2] 

机构地区：[1]重庆医科大学附属第二医院放射科,400010 [2]重庆医科大学超声影像学研究所

出　　处：《中华肝脏病杂志》2013年第1期53-56,共4页Chinese Journal of Hepatology

基　　金：重庆市卫生局医学科研计划重点项目（2011-1-052）

摘　　要：目的制备一种特异性靶向HepG2肝癌细胞株的高分子造影剂，并探讨其体外对肝癌细胞的寻靶能力。方法采用双乳化法制备高分子材料羧基端乳酸／羟基乙酸共聚物造影剂，采用碳二亚胺法将造影剂与磷脂酰肌醇蛋白聚糖-3（GPC3）抗体偶联制备出靶向高分子造影剂（GPC3-PLGA）。检测该造影剂一般特性，体外寻靶能力及靶向细胞效率，并与普通高分子造影剂做比较。结果靶向高分子造影剂的平均粒径为（800±10）nm]；体外寻靶试验显示该靶向高分子造影剂较多并牢固地聚集到肝癌细胞表面，有较强的靶向能力；流式细胞仪检测表明GPC3-PLGA微球与HepG2肝癌细胞有较强的结合能力。结论成功制备出特异性靶向肝癌细胞的高分子造影剂，该造影剂在体外对肝癌细胞具有较强的特异性结合力，有望在分子水平对肝癌的早期诊断提供一种新方法。Objective To prepare a specific high molecular weight polymer contrast agent capable of specifically targeting hepatocarcinoma cells （HCC） and to investigate its affinity in vitro using HepG2 cells. Methods The high molecular weight polymer polylactic-co-glycolic acid （PLAG）-COOH was prepared by the double emulsion technique. PLAG-COOH microbubbles were combined with glypican-3 （GPC3） antibody to generate HCC targeting high molecular polymer ultrasound contrast agents by the carbodiimide method. The affinity for HCC cells was confirmed by measuring attachment to cultured HepG2 cells by flow cytometry and comparing the results with the properties observed for non-targeted high molecular weight polymer ultrasound contrast agents. Results The average diameter of the targeted high molecular weight polymer ultrasound contrast agents was （800± 10）nm. In vitro targeting of HepG2 cells showed that many of the targeted high molecular weight polymer ultrasound contrast agents attached tightly to the cell surface and that the GPC3- PLGA has a particularly strong targeting ability. Conclusion A HCC-specific high molecular contrast agent, GPC3-PLGA, was synthesized and evidenced a strong targeting ability towards HepG2 cells in vitro. This new agent may be exploited to improve diagnosis of liver cancer at the molecular level.

关 键 词：肝肿瘤 分子靶向治疗 高分子造影剂 GPC3抗体 

分 类 号：R735.7[医药卫生—肿瘤]