非金属-有机配位键用于pH响应和肿瘤靶向药物传递的研究

项目名称： 非金属-有机配位键用于pH响应和肿瘤靶向药物传递的研究

项目编号： No.21301191

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 数理科学和化学

项目作者： 邢磊

作者单位： 中国药科大学

项目金额： 25万元

中文摘要： pH-响应性药物传递系统是近年来人们研究的热点，主要利用化学键（包括静电作用力、疏水力、氢键、共价键等）的形成与破坏构筑pH响应性药物释放系统。在对金属-有机配位键的pH响应性释放体系研究的基础上，本项目是基于非金属-有机配位键的pH响应性释放体系，以聚乙烯醇（PVA）和官能化PVA（fPVA）为载体，嫁接PEG化靶分子叶酸(FA)，以硼替佐米为模型药物，通过硼酸和邻二醇/胺的配位来装配药物，设计并合成用于卵巢癌靶向化疗的新型pH响应性前药聚合物"FA-PEG-g-fPVA-BTZ"，通过药物的疏水作用自组装成纳米颗粒，研究其在卵巢癌靶向化疗中的作用机制。通过对卵巢癌SKOV3细胞体外靶向抑制试验证实其主动靶向结合和抑制作用；通过在体试验和小鼠卵巢癌荷瘤模型，观察其体内代谢过程和主动靶向治疗卵巢癌的应用价值，为构建新型高效低毒的卵巢癌化疗药物靶向输送系统提供理论指导和实验依据。

中文关键词： pH响应性；配位键；硼酸；肿瘤治疗；药物传递

英文摘要： pH-Responsive systems have attracted the interest of a broad range of researchers in recent years. The forces that give rise to pH responses are limited to the formation or destruction of chemical interactions, such as electrostatic interactions, hydrophobic effects, and hydrogen bond, covalent bond et al. Based on metal-organic coordination bond for pH-responsive drug delivery system, the idea of this project is based on non-metal-organic coordination bond for pH-responsive drug delivery system, in which polyvinyl alcohol (PVA) and functional PVA (fPVA) were chosen as the carriers and grafted PEG-Folic acid (FA) with FA targeting moiety. Bortezomib (BTZ) as the first-in-class proteasome inhibitor was chosen as a model drug. By loading anticancer drugs through the coordination bond interaction between boron and fPVA, we designed and synthesized a novel pH-responsive prodrug polymer FA-PEG-g-fPVA-BTZ for targeting ovarian cancer,and then the prodrug polymer self-assembled into nanoparticles by means of hydrophobic interaction of anticancer drugs. we expected to study the mechanism of the nanoparticles' targeted therapeutic effct on ovarian cancer. Furthermore, we expected to demonstrate active by targeting combination and inhibition of the nanoparticles targeting inhibition test on the ovarian cancer SKOV3 cell

英文关键词： pH-responsiveness；coordination bond；Boric acid；cancer therapy；drug delivery