基础医学与临床 ›› 2011, Vol. 31 ›› Issue (7): 751-755.

• 研究论文 • 上一篇    下一篇

MUC1靶向性载药纳米粒的构建及其体外抗肿瘤效应的评估

于琛琛1,胡燕1,段金虹1,王琛2,许海燕1,杨先达1   

  1. 1. 中国医学科学院基础医学研究所
    2. 国家纳米科技中心
  • 收稿日期:2011-04-18 修回日期:2011-05-05 出版日期:2011-07-05 发布日期:2011-07-05
  • 通讯作者: 杨先达 E-mail:ayangmd@gmail.com
  • 基金资助:
    国家重大科学研究计划项目;国家自然科学基金

Preparation of MUC1-Targeted Nanoparticles and Evaluation of Its Cytotoxicity In Vitro

Chen-chen YU1,Yan HU2,Jin-hong DUAN2,Chen WANG3,Hai-yan XU1,Xian-da YANG1   

  1. 1. Institute of Basic Medical Sciences, CAMS & PUMC
    2.
    3. National Center of Nanoscience and Technology
  • Received:2011-04-18 Revised:2011-05-05 Online:2011-07-05 Published:2011-07-05
  • Contact: Xian-da YANG E-mail:ayangmd@gmail.com

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。

关键词: MUC1, 核酸适配体, 靶向给药, 肿瘤

Abstract: Objective To construct MUC1-targeted nanoparticles and evaluate its cytotoxicity in vitro. Methods MUC1 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 (P < 0.01) , 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.

Key words: MUC1, Aptamer, Targeted drug delivery, Tumor