智能型聚合物-抗体-药物偶联物的合成用于抗肿瘤药物的靶向输送和释放

本项目拟探索智能型聚合物-抗体-抗肿瘤药物偶联物（简称“聚合物-ADC”）的合成及性能。利用化学修饰方法，对抗体和抗肿瘤药物进行修饰，使它们含有可以与聚合物键合的基团。利用开环聚合、“Click”反应、有机化学反应和聚合物后修饰等方法相结合，选择临床使用的抗肿瘤药物为模型，通过刺激响应性基团将药物和抗体与生物相容和生物可降解的聚合物键合，获得一类新型聚合物-ADC。这类聚合物-ADC能够在水溶液中自组装，形成以疏水药物为核、亲水聚合物为壳的纳米粒子，抗体位于纳米粒子表面。也可以用于包覆疏水性抗癌药物，用以提高载药量、控制药物释放速率和提高药物的生物利用度。系统研究抗体和药物在聚合物分子上的键合位置，反应条件、聚合物结构与分子量、抗体分子量、连接基团、自组装结构对药物控释和肿瘤细胞增殖的抑制作用。本项目对于发展新型聚合物-ADC具有重要的理论意义和潜在的应用价值。

This project aims to explore the synthesis and properties of intelligent polymer-antibody-antineoplastic drug conjugates (referred to as "polymer-ADC"). At first, antibodies and anticancer drugs are chemically modified to contain functional groups that can bind to polymers. Subsequently, a new type of polymer-ADC will be synthesized by using ring-opening polymerization, Click reaction, organic chemical reaction and post-modification of polymers. The anticancer drugs used in clinic will be selected as models, and the drugs and antibodies will be bonded with biocompatible and biodegradable polymers by stimulus-responsive groups. This kind of polymer-ADC can self-assemble in aqueous solution to form nanoparticles with hydrophobic drug core and hydrophilic polymer shell. The antibody is located on the surface of nanoparticles. It can also be used to encapsulate hydrophobic anticancer drugs to increase drug loading, control drug release rate and improve bioavailability. The effects of various factors on the anti-tumor, including binding sites of antibodies and drugs on macromolecules, reaction conditions, polymer structure and molecular weight, molecular weight of antibodies, binding groups and self-assembly structures, will be systematically studied. This project has important theoretical significance and potential applications for the development of new polymer-ADC.