叶酸靶向修饰纳米粒加载5-氟尿嘧啶治疗胆管癌的实验研究  

5-fluorouracil carrying nanoparticles with folate-targeted modification for cholangiocarcinoma: an experimental study

作　　者：李永盛[1] 江翰[1] 王子豪[1] 施伟斌[1] 

机构地区：[1]上海交通大学医学院附属新华医院普通外科,上海200092

出　　处：《中国普通外科杂志》2013年第8期976-981,共6页China Journal of General Surgery

基　　金：上海市科委纳米专项资助项目(11nm0503700)

摘　　要：目的:探讨叶酸修饰纳米粒(药物载体)载5-氟尿嘧啶(5-FU)对胆管癌的疗效及安全性。方法:用MTT法检测无修饰和叶酸修饰纳米粒及两者加载5-FU对胆管癌QBC939细胞体外生长的影响;在荷QBC939细胞移植瘤裸鼠模型上,以生理盐水为对照,比较5-FU,载5-FU纳米粒,载5-FU叶酸修饰纳米粒对移植瘤的抑制作用;用不同浓度的叶酸修饰纳米粒孵育大鼠肝脏BRL3A细胞和肾脏NRK细胞24 h,观察其毒性作用。结果:体外实验表明,无论纳米粒修饰与否,对QBC939细胞生长均无明显影响,但两者载5-FU后对细胞生长的抑制作用均明显强于单独的5-FU作用,且载5-FU叶酸修饰纳米粒的作用更为明显(均P<0.05);5-FU,载5-FU纳米粒,载5-FU叶酸修饰纳米粒对移植瘤生长的抑制率分别为56.0%,61.5%,74.4%,各组间差异均有统计学意义(均P<0.05);与不同浓度叶酸修饰纳米粒孵育后,BRL3A细胞和NRK细胞的形态均无明显改变。结论:叶酸修饰的纳米载药系统具有良好的特异性、靶向性及生物安全性,叶酸修饰载5-FU纳米粒对胆管癌有良好的疗效。Objective：To investigate the effect of the folate-conjugated nanoparticles（drug carrier） loaded with 5-fluorouracil（5-FU） against bile duct carcinoma and its safety.Methods：The effects of nanoparticles without modification and folate-conjugated nanoparticles or their 5-FU loaded ones on the growth of the cholangiocarcinoma QBC939 cells in vitro were determined by MTT assay.In nude mice bearing QBC939 cell grafts,the inhibitory effects on the tumor grafts among 5-FU,5-FU loaded nanoparticles and 5-FU loaded folate-conjugated nanoparticles were compared using normal saline as a control.The toxic effects of the folate-conjugated nanoparticles were tested by incubation of the rat liver BRL3A cells and renal NRK cells with different concentrations of the folate-conjugated nanoparticles for 24 h.Results：The in vitro experiments showed that both nanoparticles with or without modification exerted no obvious influence on the growth of QBC939 cells,but both had stronger inhibitory effects than that of 5-FU alone on the growth of QBC939 cells after they were loaded with 5-FU,which was more evident for the folate-conjugated nanoparticles（all P＆lt;0.05）.The suppression ratios of the tumor grafts in nude mice for 5-FU,5-FU loaded nanoparticles and 5-FU loaded folate-conjugated nanoparticles were 56.0%,61.5% and 74.4% respectively,and the differences among them had statistical significance（all P＆lt;0.05）.There were no morphological changes in BRL3A cells or NRKP cells after exposure to any of the used concentrations of folate-conjugated nanoparticles.Conclusion：The drug delivery system of folate-conjugated nanoparticles has favorable and specific targeting characteristcs,and shows remarkable therapeutic potential for cholangiocarcinoma after it is loaded with 5-FU.

关 键 词：胆管肿瘤 药物疗法 纳米粒子 叶酸 小鼠 裸 

分 类 号：R735.8[医药卫生—肿瘤]