基于RNA aptamer主动靶向于肿瘤干细胞的纳米金载药系统的构建和研究

项目名称： 基于RNA aptamer主动靶向于肿瘤干细胞的纳米金载药系统的构建和研究

项目编号： No.81202484

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 药物学、药理学

项目作者： 李磊

作者单位： 大连医科大学

项目金额： 23万元

中文摘要： 拟回答的科学问题：现认为肿瘤干细胞是肿瘤形成及其不断生长的根源，在启动肿瘤形成和生长中起着决定性的作用。如何将药物载入到肿瘤干细胞中，从根本上清除肿瘤干细胞是问题所在。目的：构建一个主动靶向于肿瘤干细胞的功能型纳米金载药传递系统，能够避开体内网状内皮系统的吞噬，富集于肿瘤组织中，由于主动靶向的aptamer识别分子的作用，纳米粒通过内吞作用进入靶细胞，在胞内微酸性的环境下（pH4.5~5.5左右）快速释药，消除肿瘤干细胞。内容：（1）构建抗肿瘤干细胞纳米粒；（2）利用荧光活化细胞分选系统（FACS）进行肿瘤干细胞的筛选与识别；（3）肿瘤细胞的MTT研究和纳米粒的肿瘤干细胞靶向性研究；（4）动物肿瘤移植模型中的纳米粒的疗效评价；（5）构建纳米粒在动物体内的药动学和组织分布。意义：探索新的抗肿瘤思路，扩大了药效和毒副作用均较强的药物的应用范围，对靶向肿瘤干细胞的制剂研究提供了新的方向和方法。

中文关键词： 靶向纳米粒；核酸适配体；双载药纳米粒； 上皮细胞粘附因子；多药耐药蛋白

英文摘要： The scientifical problem should be answer: Recently it was considered that cancer stem cell was the source of tumor formation and growth, and plays a crucial role in the trigger tumor formation and growth.The important problem was how to release the chemodrug into the cancer stem cells for eradication tumor radically.Aim: the subject intends to build a functional gold nanoparticles of drug delivery system with active targeting to cancer stem cell.The nanoparticles can avoid the phagocytosis effect of RES, concentrate on tumor tissues, and pass through into the target cells with endocytosis because of the specific binding of aptamer as recognition molecules with the cancer cells in which drug release quickly for the acidic environment (pH4.5 ~ 5.5). Content:(1)Construction of nanoparticle targeting to cancer stem cells;(2)Separation and Identification of cancer stem cells by FACS system;(3)The MTT research of cancer cells and the targeting research of nanoparticle to cancer stem cells;(4)Therapeutic evaluation of nanoparticle in animal xenograft tumour models;(5)The research of pharmokinetic and tissue distribution in animals for nanoparticle.Meaning: New idea for anticancer is provided.The extend of application for the drug which has strong potency and side effects is increased. New method and direction are pro

英文关键词： Targetd nanoparticle；Aptamer；co-delivery nanoparticle；EpCAM；MDR