间接抑制受体相关蛋白以增强抗肿瘤转移效果的靶向脂质体的构建及机制研究

项目名称： 间接抑制受体相关蛋白以增强抗肿瘤转移效果的靶向脂质体的构建及机制研究

项目编号： No.81503011

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 秦超

作者单位： 中国药科大学

项目金额： 17.9万元

中文摘要： 配体修饰的纳米载体通过肿瘤细胞特异性受体蛋白介导入胞，实现药物靶向递送。同时，细胞膜蛋白种类丰富并常以复合体或脂伐等形式共同发挥作用，但是载体在介导入胞时是否会影响受体相关蛋白的功能目前并不清楚。本项目以氯毒素（CTX）修饰的脂质体为纳米载体，提出一种新的肿瘤治疗策略，利用CTX可以间接抑制脑胶质瘤特异性表达的ClC-3离子通道蛋白的特点，在修饰脂质体经MMP-2受体介导增加摄取的同时，间接作用于ClC-3通道蛋白，抑制细胞迁移能力，起到抗肿瘤转移作用，从而增强系统的抗肿瘤效果。此外，本研究利用原位胶原酶谱法等技术手段对修饰脂质体同ClC-3的作用机制进行研究，从分子生物水平对修饰脂质体的抗转移作用进行机理阐述。本项目设计思路、研究手段等国内外未见报道，项目新颖性好，科研条件具备，有关工作基础较扎实，已有工作基础表明本项目的可行性良好。

中文关键词： 脂质体；抗肿瘤效果；受体介导

英文摘要： Currently, it is unknown whether a receptor-associated protein will be affected when a ligand modified delivery system interacts with its receptor. In this project, a new anti-tumor active targeting strategy was proposed. In this strategy, the modified liposomes expressed targeting property to increase the toxicity against the cancer cells and inhibited the migration of the cells by affecting the receptor associated membrane protein at the same time. In detail, the chlorotoxin-modified on the surface of liposomes can inhibit the function of receptor-associated protein ClC-3 to enhance the anti-metastasis efficiency of the liposomes when it binds to its receptor MMP-2. The interdisciplinary technology and the design ideas have not been reported. We not only have strong related research-force, but also possess perfect research-conditions for the project. Moreover, the base of relevant work for the project has been established, indicating the feasibility of this project.

英文关键词： liposomes;antitumor efficiency;receptor-mediated