叶酸修饰多西紫杉醇纳米脂质体对肝癌Bel-7402细胞的体内外靶向性研究  

Study on Targeting of Folic Acid-modified Docetaxel Nano-liposome to Hepatocellular Carcinoma Bel-7402 Cells in vivo and in vitro

作　　者：计竹娃[1] 钦富华[1] 夏晓静[1] 胡英[1] 

机构地区：[1]浙江医药高等专科学校生物与制药学院,浙江宁波315100

出　　处：《中国药房》2016年第10期1325-1328,共4页China Pharmacy

基　　金：浙江省科技厅公益性技术应用研究计划项目(No.2014C33225);宁波市科技局一般科研立项项目(No.2015C110027)

摘　　要：目的:研究叶酸(FA)修饰多西紫杉醇(DOC)纳米脂质体(L-DOC-FA)对肝癌Bel-7402细胞的体内外靶向性。方法:采用细胞活性检测试剂盒分别检测0、1、2、5、10、20μg/ml DOC、L-DOC、L-DOC-FA培养细胞24 h后的细胞活性,计算细胞存活率;利用荧光素异硫氰酸酯标记L-DOC、L-DOC-FA,检测肝癌细胞Bel-7402对L-DOC、L-DOC-FA的摄取率;125I标记L-DOC、L-DOC-FA,检测其在皮下肿瘤组织中的含量;取28只Balb/c裸鼠,背部ih肝癌细胞悬液复制肿瘤模型,模型复制成功后将裸鼠分为空白对照(生理盐水)组、DOC(3 mg/kg)、L-DOC(3 mg/kg,以DOC计)和L-DOC-FA(3 mg/kg,以DOC计)组,每天尾iv相应药物1次,连续30 d,测定各组裸鼠肿瘤的相对瘤体积。结果:DOC、L-DOC、L-DOC-FA对肝癌Bel-7402细胞活性均有抑制作用,细胞存活率降低且呈浓度依赖性;与DOC、L-DOC比较,L-DOC-FA作用后细胞活性更低,细胞存活率降低(P<0.01)。细胞对L-DOC、L-DOC-FA的摄取率大小为L-DOC-FA(69.5%)>L-DOC(31.2%),差异有统计学意义(P<0.01);肿瘤组织中L-DOC-FA含量比L-DOC含量高(P<0.01);3 mg/kg L-DOC-FA比相同质量浓度L-DOC、DOC抑瘤效果更明显,相对瘤体积更小(P<0.01)。结论:L-DOC-FA在体内外均对肝癌Bel-7402细胞有明显的主动靶向性,并表现出了很好的体内外肿瘤靶向抑制效果。OBJECTIVE：To study the targeting of folic acid（FA）-modified docetaxel（DOC）nano-liposome（L-DOC-FA）to hepatocellular carcinoma Bel-7402 cells in vivo and in vitro. METHODS：The cell viability and survival rate of Bel-7402 cells was tested by CCK-8 kit after treated with 0,1,2,5,10 and 20 μg/ml DOC,L-DOC and L-DOC-FA for 24 h. And then,the fluorescein isothiocyanate was used to label L-DOC and L-DOC-FA nano-liposome,and the rate of L-DOC and L-DOC-FA absorbed by hepatocellular carcinoma Bel-7402 cells were detected.125 I was used to label L-DOC and L-DOC-FA nano-liposome,and then the contents of them in the subcutaneous tumor tissues were detected. 28 Balb/c naked mice were selected and given liver cell suspension via back ih to induce tumor model. After modeling,naked mice were divided into blank control group（normal saline）,DOC group（3 mg/kg）,L-DOC（3 mg/kg,by DOC）and L-DOC-FA（3 mg/kg,by DOC）. They were given relevant medicine intravenously once a day for consecutive 30 d. The relative tumor volume in naked mice was detected. RESULTS：DOC,L-DOC and L-DOC-FA all inhibited the cell viability of Bel-7402 cells,the survival rate of cells decreased in concentration-dependant manner;compared with DOC and L-DOC,the cell viability decreased after treated with L-DOC-FA,the survival rate of cells decreased（P0.01）. The rate of L-DOC and L-DOC-FA absorbed by Bel-7402 cells in descending order as L-DOC-FA（69.5%）L-DOC（31.2%）,with statistical significance（P0.01）. The content of L-DOC-FA in tumor was significantly more than that of L-DOC（P0.01）. In addition,3 mg/kg L-DOC-FA showed better inhibitory effect than 3 mg/kg L-DOC and DOC on tumor,and the relative tumor volume was smaller（P0.01）. CONCLUSIONS：L-DOC-FA has obvious targeting to Bel-7402 cells in vivo and in vitro,and shows good inhibitory effect on tumor in vivo and in vitro.

关 键 词：叶酸修饰纳米脂质体 多西紫杉醇 靶向性 肝癌BEL-7402细胞 肿瘤抑制 裸鼠 

分 类 号：R965[医药卫生—药理学]