生物响应、多功能脂质-聚合物杂化纳米药物输送系统研究

项目名称： 生物响应、多功能脂质-聚合物杂化纳米药物输送系统研究

项目编号： No.51473127

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： 黄世文

作者单位： 武汉大学

项目金额： 85万元

中文摘要： 化疗作为临床上治疗癌症的最重要手段之一,目前面临的最大难题是化疗药物在杀死肿瘤细胞的同时损害健康细胞，造成毒副作用。生物响应性纳米载体为肿瘤化疗提供新的思路。本项申请拟发展一种构建生物响应脂质-聚合物杂化纳米粒子的新方法，在此基础上，针对肿瘤微环境的化学特性和肿瘤化疗的特点，分别研究具有还原响应、pH敏感和氧化响应的脂质-聚合物杂化纳米药物载体。系统表征杂化纳米载体的理化性能、响应性药物释放性质，在细胞水平研究抗肿瘤效果及载药杂化纳米粒子与肿瘤细胞的相互作用、细胞摄取行为及其在肿瘤细胞内的转运等，在整体动物水平研究药物分布、抗肿瘤生长能力；进一步将具有肿瘤靶向特性的靶向基团引入脂质，构建具有肿瘤靶向能力的生物响应脂质-聚合物杂化纳米载体；为了发展具有造影能力的纳米药物载体，将含钆-DTPA配合物的两亲性脂质引入杂化纳米粒子，制备高效、多功能的纳米药物载体。

中文关键词： 药物载体；纳米粒子；肿瘤靶向；控制释放；生物可降解高分子

英文摘要： The greatest challenge of chemotherapy, one of the most important methods for the clinical treatment of cancers, is that the chemotherapeutics hurt the healthy cells. Nanosized anticancer drug, especially biologically responsive nano drugs, improves the accumulation of drug in tumor and improves the efficiencies of anticancer with lower toxicity and other side effects.The aim of this project is to develop a novel method for the construction of biologically responsive lipid-polymer hybrid nanocarriers, including reduction-sensitive, pH sensitive and oxidation sensitive hybrid nanoparticles, for anticancer drug delivery.It is necessary to study the physical-chemical characteristic of the hybrid nanoparticles and responsive release of anticancer drug from the hybrid nanocarrier, and in cell level and animal level, study the interaction between the responsive hybrid nanoparticles and cells.Furthermore, tumor targeted nanocarriers and MRI-guiding funtionalized responsive lipid-polymer hybrid nanocarriers will also be designed based on this technique.The deep understanding of the relationship between the structures of responsive PEG containing lipid and antitumor ability is expected to provide the chance to develop the new generation of nanomedicine for cancer therapy.

英文关键词： drug carrier;hybrid nanoparticle;tumor targeting;controlled release;biodegradable polymer