基于金属有机骨架结构的新型类高分子胶束载药系统的研究

Polymer micelles have received much attention as drug delivery carriers, however, the low drug loading limits their clinical application in cancer chemotherapy. In this project, a novel analogous-polymer-micelle drug delivery system with metal organic framework is designed. Metal-organic framework with high porosity is formed by the coordination between metal ions (zinc ion , Ferric ion etc.)and small molecule organic ligands(bix, 1,4-BDC etc.). The analogous polymer micelle is formed by the coordination reaction between the empty orbital of the metal ions in metal organic framework and the terminal thiol of PEG (or PVP) containing pH-sensitive bonds(the hydrazone or ortho ester bond). Its structure is composed of metal organic framework for the core and PEG(or PVP) for the shell. A large number of anticancer drugs are loaded into the analogous polymer micelle by the high porosity of metal organic framework and π-π interaction between the small molecule organic ligands and anticancer drugs. A multifunctional analogous-polymer- micelle drug delivery carrier is built with long cycle, high drug loading and pH sensitivity in order to solve the problem of low drug loading, which provides new ideas and methods for the design of the polymer micelle drug delivery system.

高分子胶束抗肿瘤药物传输系统的研究受到了广泛的关注，然而载药量低是限制其在肿瘤化疗临床应用的主要障碍。本项目拟设计构建一类新型的基于有机金属骨架的类高分子胶束载药系统。通过金属离子（锌离子、三价铁离子等）和小分子有机配体（1,4-二（咪唑基甲基）苯（bix）、1,4-对苯二甲酸（1,4-BDC）等）之间的配位作用形成具有高孔隙率的金属有机骨架。利用金属离子的空轨道和带有pH敏感键（腙键、原酸酯键）的PEG（或PVP）端巯基的配位作用形成以金属有机骨架为核，PEG（或PVP）为壳的具有类似于高分子胶束壳核结构的纳米粒子。通过金属有机骨架中高的孔隙率以及小分子有机配体与抗肿瘤药物间的π-π作用大量装载抗肿瘤药物，构建具有长循环、高载药量和pH敏感等多种功能的类高分子胶束纳米药物传输系统，解决高分子胶束载药系统面临的载药量低的问题，为高分子胶束载药系统的设计、构建提供新思路和新方法。

高分子胶束抗肿瘤药物传输系统的研究受到了广泛的关注，然而载药量低是限制其在肿瘤化疗临床应用的主要障碍。本项目拟设计构建一类新型的基于金属有机骨架的高载量药物传递系统。通过金属离子（钆离子、三价铁离子等）和小分子有机配体（1,4-对苯二甲酸（1,4-BDC）等）之间的配位作用形成具有高孔隙率及好的水域稳定性的金属有机骨架材料。利用双模板剂调控金属有机骨架材料的孔径及其比表面积。通过金属有机骨架中高的孔隙率以及小分子有机配体与抗肿瘤药物间的π-π作用大量装载抗肿瘤药物，构建生物相容性及水域稳定性好的高载药量纳米药物传输系统，解决高分子胶束载药系统面临的载药量低的问题，为载药纳米系统的设计、构建提供新思路和新方法。