多层次智能药物传输体系的制备及其逆转多药耐药性

项目名称： 多层次智能药物传输体系的制备及其逆转多药耐药性

项目编号： No.51473165

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 一般工业技术

项目作者： 庄秀丽

作者单位： 中国科学院长春应用化学研究所

项目金额： 85万元

中文摘要： 肿瘤细胞多药耐药性是恶性肿瘤临床化学治疗失败的主要原因之一，已经成为肿瘤治疗中亟待解决的问题。通过智能药物传输体系负载和控制释放抗肿瘤药物是克服肿瘤细胞多药耐药性的一种新思路。本项目针对肿瘤细胞多药耐药性，从肿瘤组织和细胞内微环境出发，拟通过嵌段共聚物上的醛基与载药纳米凝胶表面上的氨基的席夫碱反应，制备两类外壳可脱离的药物传输体系。该多层次智能药物传输体系具有肿瘤靶向性，其载药纳米凝胶内核具有增强组织渗透、提高细胞内吞以及细胞内微环境响应性释放的能力，期望通过单克隆抗体、广谱抗肿瘤药物和P-糖蛋白抑制剂的按需释放和协同作用逆转肿瘤细胞多药耐药性，从而治疗晚期耐药性肿瘤。本项目的实施将为研制可逆转肿瘤细胞多药耐药性的具有临床应用价值的智能药物传输体系提供实验和理论基础。

中文关键词： 多层次；多药耐药性；控制释放；药物传输体系；智能性

英文摘要： Multidrug resistance (MDR) of tumor cells is one of the leading causes that induce the failure of malignancy chemotherapy, and has thus become the most urgent problem to be solved in the oncology treatment. The encapsulation and controlled delivery of antitumor drugs with intelligent drug delivery platforms is one kind of novel idea to overcome the MDR of tumor cells. Inspired from the tumor tissular and intracellular microenvironments, this project is to prepare two kinds of shell-detachable drug delivery systems through the Schiff base reaction between aldehyde group in block copolymer and amino group on the surface of drug-loaded nanogel against the MDR of tumor cells. The multi-level intelligent drug delivery systems exhibit tumor targeting, and the drug-loaded nanogel as the core of nanocarrier shows the capabilities of enhanced tumor tissue penetration and cell endocytosis, and intracellular microenvironment triggered drug release. It aims to reverse the MDR of tumor cells and treat the advanced drug resistance tumors through the on-demand release and synergistic effect of monoclonal antibody, broad-spectrum antineoplastic and P-glycoprotein inhibitor. The implementation of this project will provide the experimental and theoretical foundations for the research and development of smart drug delivery system with clinical value for overcoming MDR of tumor cells.

英文关键词： Multi-level;Multidrug resistance;Controlled release;Drug delivery system;Intelligence