包载抗肿瘤药物的聚合物纳米胶粒与P-糖蛋白的相互作用研究

项目名称： 包载抗肿瘤药物的聚合物纳米胶粒与P-糖蛋白的相互作用研究

项目编号： No.21273200

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 王琦

作者单位： 浙江大学

项目金额： 76万元

中文摘要： 癌症是人类健康的头号杀手。药物治疗过程中碰到的最大困难是耐药性问题，往往会导致化疗效果不佳甚至失败。因此，了解肿瘤细胞对化疗药物产生耐药性的原因和机制，具有重要的理论意义和现实意义。研究表明，细胞膜上的P-糖蛋白会将药物泵出细胞外，导致肿瘤耐药。聚合物纳米胶粒是近年出现的一种有抑制多药耐药性的新型药物递送系统。目前，关于抗癌药物、聚合物载体与P-糖蛋白之间相互作用的研究，主要是实验方面的工作，涉及相互作用机理和分子模拟方面的研究甚少。分子模拟是联系理论与实验之间的桥梁，是对实际实验的有力补充，其优势是可以为我们提供许多实际实验难以获得的微观信息。本项目采用分子模拟的方法研究抗癌药物、聚合物载体与P-糖蛋白之间的相互作用，通过改变聚合物聚合度、取代基团和取代位置，探究相互作用能的变化规律，揭示聚合物载体结构与抑制肿瘤多药耐药性之间的关系，为寻找抑制肿瘤多药耐药性的聚合物载体的设计提供新思路。

中文关键词： 抗肿瘤药物；聚合物纳米胶粒；P-糖蛋白；相互作用；药物递送系统

英文摘要： Cancer has been the main killer of human health. In medical treatment, the greatest difficulty encountered can be ascribed to drug resistance, which often gives rise to unfavorable effect of chemotherapy or even failure. Consequently, understanding the causes and mechanisms of the drug resistance resulting from tumor to chemotherapy drugs is of theoretical and practical significance. As studies indicate, P-glycoprotein in the cell membrane will pump drug out of the cell, causing tumor drug resistance. Polymer nanoparticles in recent years can be considered as a novel drug delivery system to inhibit the multidrug resistance. Currently, researches concerning the interaction among anti-cancer drug, polymer nanoparticles and P-glycoprotein have primarily focused on experimental results; however, work involving interaction mechanism and molecular modeling is rather scarce. Molecular simulation, which connects the theoretical and the experimental, is a strong supplement in providing detailed information in the micro scope that is hardly obtained from the actual experiments. This project aims at studying the interaction of anti-cancer drug, polymer nanoparticles and P-glycoprotein by molecular simulations. It attempts to explore interaction energy variation by changing the degree of polymerization of the polymer, subst

英文关键词： Anti-cancer drug；Polymer nanoparticle；P-glycoprotein；Interaction；Drug delivery system