叶酸修饰金属-有机骨架药物传递体的制备及主动肿瘤靶向性研究

项目名称： 叶酸修饰金属-有机骨架药物传递体的制备及主动肿瘤靶向性研究

项目编号： No.21501036

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 数理科学和化学

项目作者： 张凤鸣

作者单位： 哈尔滨理工大学

项目金额： 20万元

中文摘要： 恶性肿瘤是危害人类健康的顽症之一，化学药物治疗是治疗恶性肿瘤的重要措施，构建主动肿瘤靶向药物传递系统是全球科学家亟待解决的难题。本项目拟利用不同骨架大小双齿羧酸配体和5-醛基-1,10-菲咯啉辅配体与Zn2+, Fe3+金属离子反应，制备系列具有梯度孔道结构的纳米金属-有机骨架（MOFs）药物载体，进而利用MOFs后合成修饰的方法，通过MOFs骨架中的醛基与叶酸分子中的氨基发生席夫碱缩合反应，将叶酸修饰在纳米MOFs的表面，制备具有以叶酸受体为靶点的主动肿瘤靶向药物传递系统，考察其对特定肿瘤细胞的选择性，探究MOFs结构、纳米MOFs的形貌及叶酸修饰率等对靶向功能的影响规律。本项目旨在构建具有主动靶向功能的MOFs药物传递系统，为肿瘤治疗提供新思路，也为MOFs后合成修饰的功能化提供新方向。

中文关键词： 配合物；金属-有机骨架；后合成修饰；药物传递；肿瘤靶向

英文摘要： Malignant tumor is one of the chronic and stubborn diseases threatening human health, while chemotherapy is a very important way in the treatment of tumor. To establish active targeting drug delivery system for anti-cancer drug is a hard work for the scientists in the world. This project plans to prepare a series of porous metal-organic frameworks (MOFs) as drug-delivery nanocarriers by reacting of bidentate carboxyl acid and 1,10-phenanthroline-5-carboaldehyde with Zn2+, Fe3+ ions. Then, folic acid is modified on the surface of the nano-MOFs by Schiff base condensation reaction of aldehyde group on the framework with amino-group of folic acid. By the post-synthesis modification, the nano-MOFs drug delivery system possesses the function of active targeting to folate receptor in cancer cell, and the selectivity of the system to special cancer cell will be evaluated. The influence of structure, morphology, modification rate of folic acid to targeting function will be explored. The purposes of the project are construction drug delivery system with active targeting function, providing a new way to therapy of tumor, and developing a new field to functionality of MOFs by post-synthesis modification.

英文关键词： Complexes;Metal-Organic Frameworks;Post-Synthesis Modification;Drug Delivery;Tumor Targeting