具有靶向和量子点示踪功能的水溶性聚酯高分子键合药研究

项目名称： 具有靶向和量子点示踪功能的水溶性聚酯高分子键合药研究

项目编号： No.51273169

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 一般工业技术

项目作者： 张雪飞

作者单位： 湘潭大学

项目金额： 80万元

中文摘要： 本项目提出制备一种水溶性脂肪族聚酯，侧链键接具有反应活性的亲水基团（如羟基、羧基），在此基础上将叶酸靶分子和量子点通过化学修饰键合到聚合物链的端基上，以达到药物的靶向给药和荧光标记示踪作用，同时通过选择不同的化学键（腙键、酯键、二硫键）来进行抗肿瘤药物分子与聚合物侧基官能团的键合反应，以实现药物在肿瘤组织所具有的特定的生理微环境下的智能释放（如低pH，还原性环境），最终制备一种水溶性的、可降解和具有良好生物相容性的，具有靶向、示踪和智能释放功能的抗肿瘤药物载体和键合药，并对其自组装行为，体外药物释放行为和材料降解行为进行研究，通过体外细胞和体内细胞实验，对其细胞毒性和细胞靶向行为进行研究，并通过量子点的荧光成像，研究这载药体系的细胞内吞和体内摄入行为，和在肿瘤细胞与组织中的富集及体内循环行为，探讨其作用机理与影响因素，为进一步设计与制备新型药物载体和给药体系提供依据和指导。

中文关键词： 脂肪族聚酯；量子点；生物素；前药；诊断治疗一体化纳米平台

英文摘要： The project was proposed to prepare a kind of water-soluble aliphatic polyester, which have reactive hydrophilic group (such as hydroxyl and carboxyl group) in the side chain. Furthermore, folic acid as targeting molecule and quantum dots as fluorescent labeling and tracing role could be conjugated in the terminal group. Anticancer drug could be conjugated to side groups on the polymer via stimuli-responsive chemical bond (such as hydrazones, ester or disulfide), in order to controll the drug release behavior under specific physiological microenvironment (such as low pH, reducing environment). And finally, a novel anticancer drug carrier and conjugate were prepared with good water-solubility, biocompatibility, and biodegradability, which provides several unique properties such as targeting delivery, fluorescent labeling and tracing role, and intelligent release. The self-assembly, drug release assessment and material degradation behavior in vitro should be studied. The cytotoxicity and cell-targeted behavior will also be conducted in vitro and vivo. Meanwhile, with fluorescence imaging technology through quantum dots, the endocytosis of cell, intake behavior, enrichment in the tumor cell and tissue, and the behavior of circulating in vivo should be studied, which should contribute to discover the mechanism and t

英文关键词： aliphatic polyester；quantum dots；biotin；prodrug；theranostic nanoplatforms