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.
出处
《中国普通外科杂志》
CAS
CSCD
北大核心
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)
关键词
胆管肿瘤
药物疗法
纳米粒子
叶酸
小鼠
裸
Bile Duct Neoplasms/drug ther
Nanoparticles
Folic Acid
Mice,Nude