MUC1靶向性载药纳米粒的构建及其体外抗肿瘤效应的评估  

Preparation of MUC1-targeted nanoparticles and evaluation of its cytotoxicity in vitro

作　　者：于琛琛[1] 胡燕[1] 段金虹[1] 王琛[2] 许海燕[1] 杨先达[1] 

机构地区：[1]中国医学科学院基础医学研究所,北京100005 [2]国家纳米科学中心,北京100190

出　　处：《基础医学与临床》2011年第7期751-755,共5页Basic and Clinical Medicine

基　　金：国家重大科学计划(2011CB911003;2011CB911004;2011CB933504);国家自然科学基金(81071870)

摘　　要：目的构建MUC1靶向纳米粒,并在体外评估其抗肿瘤效应。方法 采用聚乳酸聚乙醇酸共聚物(PLGA)制备包载紫杉醇的纳米粒,并在表面偶联具有MUC1蛋白靶向性的核酸适配体。紫外分光光度法、动态光散射法测定MUC1靶向载药纳米粒的基本表征;以MUC1过表达的乳腺癌细胞MCF-7为实验组,肝癌细胞HepG2为对照组,用流式细胞仪检验纳米粒的选择性,MTS法评估其杀伤效果和IC50。结果 MUC1靶向载药纳米粒粒径(225.3±9.2)nm,药物包封率83.6%±1.7%,在体外可以特异性地被MUC1+癌细胞摄入,对MCF-7细胞杀伤作用显著强于普通载药纳米粒(P<0.01),IC50为1.52 mg/L。结论 该靶向纳米粒可以在体外特异性地增加MUC1+肿瘤细胞对纳米粒的摄入,降低IC50值,提高抗化疗药物对肿瘤细胞的杀伤效率。Objective To construct MUC1-targeted nanoparticles and evaluate its cytotoxicity in vitro.MethodsMUC1 aptamers were conjugated to the surface of nanoparticles which were made of poly（lactic-co-glycolic-acid）（PLGA） nanoparticles and loaded with paclitaxel（PTX）.The MUC1-targeted nanoparticles（Apt-NP-PTX） were characterized by UV spectrophotometry and dynamic light scattering.Using MUC1-overexpressing MCF-7 breast cancer cell as experimental group,and HepG2 as control group,the specificity of the Apt-NP-PTX was detected by flow cytometry.The cytotoxicity and IC50 of Apt-NP-PTX against MCF-7 were evaluated using a standard MTS assay.Results The Apt-NP-PTX were about（225.3±9.2） nm in size with an encapsulation efficiency of 83.6%±1.7%.The Apt-NP-PTX enhanced in vitro drug delivery and cellular toxicity to MUC1＋ cancer cells,as compared with non-targeted nanoparticles that lack the MUC1 aptamer（P0.01）,with IC50 of 1.52 mg/L and 4.10 mg/L,respectively.Conclusion The Apt-NP-PTX can effectively enhance the PTX delivery to MUC1-overexpressing MCF-7 cells in vitro.

关 键 词：MUC1 核酸适配体 靶向给药 肿瘤 

分 类 号：R73-3[医药卫生—肿瘤]