叶酸靶向长春新碱纳米微球对腺样囊性癌细胞活性的影响  

Effect of folic acid targeted vinscristine-loaded nanopaticles on adenoid cystic carcinoma cell activity

作　　者：林婷婷[1] 何彦津[1] 朱利民[1] 罗浩[2] 常津[2] 张虹[3] 张红梅[3] 

机构地区：[1]天津医科大学眼科中心,天津市300070 [2]天津大学,天津市300072 [3]天津医科大学第二医院眼科,天津市300211

出　　处：《眼科新进展》2010年第4期335-340,共6页Recent Advances in Ophthalmology

基　　金：天津市卫生局科技基金项目(编号:05kyz64);叶酸-长春新碱靶向缓释纳米微球制备方法及用途(专利号:200910069696.2)~~

摘　　要：目的制备连接有叶酸（folic acid,FA）的长春新碱（vinscristine,VCR）靶向缓释纳米微球（nanopaticles,NP）FA-PLGA（VCR）-NP,观察其表征及对体外培养的腺样囊性癌低转移株（adenoid cystic carcinoma,ACC-2）细胞增殖的抑制作用。方法采用改良的复乳法制备FA-PLGA（VCR）-NP,测定NP的粒径分布、载药率及体外释放曲线等;MTT比色法检测高浓度下的PLGA-NP对肿瘤细胞的毒性作用,比较药物组VCR、PLGA（VCR）-NP、FA-PLGA（VCR）-NP3种药物在不同浓度和不同作用时间对ACC-2细胞的抑制作用;异硫氰荧光素标记PLGA-NP和FA-PLGA-NP,荧光显微镜观察FA-PLGA-NP的靶向性及游离FA对其影响。结果FA-PLGA（VCR）-NP形态圆整,大小均匀,平均粒径249.2nm,载药率4.5%,体外释放时间达14d;PLGA-NP与ACC-2细胞共培养5d,细胞存活率达80.0%以上;给药后第4~5天FA-PLGA（VCR）-NP对ACC-2细胞的抑制率显著高于VCR,3种药物对细胞抑制作用均呈时间和浓度依赖性;FA-PLGA-NP可靶向附着于ACC-2细胞表面,这种识别可以被FA竞争性抑制。结论FA-PLGA（VCR）-NP具有稳定的载药率和体外释放行为,具有良好的靶向识别力,体外实验证实具有优于VCR原药的抗肿瘤能力。Objective To investigate the characteristics of folic acid（FA）targeted vinscristine（VCR）-loaded nanopaticles（NP）（FA-PLGA（VCR）-NP）and its inhibitive effects on adenoid cystic carcinoma（ACC-2）cell proliferation in vitro.Methods FA-PLGA（VCR）-NP was prepared by multiple emulsion technique.Particle size,drug loading rate and releasing curve in vitro of NP were detected.MTT colorimetry was used to measure the toxicity of PLGA-NP with high concentration on tumor cells.The inhibitive effects of VCR,PLGA（VCR）-NP and FA-PLGA（VCR）-NP at different concentrations and different time points on ACC-2 in drug groups.PLGA-NP and FA-PLGA-NP were marked by fluorescein isothiocyanate.Fluorescene microscope was used to observe the target of FA-PLGA-NP and effects of free FA on FA-PLGA-NP.Results FA-PLGA（VCR）-NP was in round shape and even size with a mean particle size at 249.2 nm,the drug loading rate was 4.5%,and the releasing time in vitro was 14 days.After PLGA-NP and ACC-2 co-cultured for 5 days,cell survival rate had remained at more than 80%.The inhibitive rate of FA-PLGA（VCR）-NP on ACC-2 was obviously higher than that of VCR at the 4th to 5th day after giving drugs.The inhibitive effects of three drugs were in dose-dependent and time-dependent manners.FA-PLGA-NP could targeted adhere to cell surface of ACC-2,which could be competitively inhibited by FA.Conclusion FA-PLGA（VCR）-NP has a stable drug loading rate and releasing behavior in vitro,better targeted recognition,and is with a better anti-tumor effect than VCR in vitro.

关 键 词：腺样囊性癌 长春新碱 叶酸 纳米微球 细胞活性 

分 类 号：R730.26[医药卫生—肿瘤] R77[医药卫生—临床医学]