聚磷酸酯大分子前药的合成及抗肿瘤活性研究

The design and synthesis of polymeric materials for smart drug delivery system is one of the important fields in polymer science. When the hydrophilic or amphiphilic polymers are used to load drugs, the drug loading efficiency is usually low. To increase the drug loading efficiency, a new kind of polyphosphate macromolecular prodrugs will be developed in this project. First, a series of macromolecular prodrugs will be prepared through ring-opening polymerization of different cyclic phosphate drug monomers. By adjusting the structures of cyclic phosphate drug monomers, topological structures of macromolecular prodrugs will be controlled, including linear/linear block, hyperbranched multiarm structure and nanogel. Because the drugs are as a part of the monomers, the drug loading efficiency can be increased in these polymers. And then, in vitro and in vivo anti-cancer activity evaluation of these macromolecular prodrugs will be investigated. Finally, other functional groups can be attached to the macromolecular prodrugs through the reaction with active sites in the polymer. These polyphosphate macromolecular prodrugs nanomaterials can be used as drug carriers for tumor therapy, and open a window for designing polymer drug carriers.

设计合成用于智能药物输送系统的聚合物材料是高分子科学领域的重要研究领域之一。现有研究主要是利用亲水性聚合物嵌段对药物进行共价修饰，或利用两亲性的聚合物包埋药物，载药率通常较低。本项目拟利用含有顺铂的环状磷酸酯作为单体，直接合成聚磷酸酯大分子前药，以实现药物的高效负载。拟合成不同结构的含有顺铂的环状磷酸酯单体，用含有聚乙二醇或者自身引发开环聚合反应，获得一系列不同拓扑结构的聚磷酸酯大分子前药。通过优化反应条件，探索聚合物合成的最佳途径。进而对聚合物进行体外和体内的生物活性评价，实现对肿瘤的治疗。最后，利用聚合物的羟基反应位点，引入功能基团，实现对于肿瘤的诊断和治疗结合在一起的个性化治疗。上述的研究，可为聚合物药物载体的设计提供新的思路。

构筑用于智能药物输送系统的材料是高分子科学，乃至化学领域的重要研究热点之一。本项目开展了基于两亲性大分子的自组装及其作为前药的抗肿瘤活性的研究。通过本项目，我们进一步发展用于药物输送载体的聚磷酸酯材料，丰富了两亲性药-药缀合物药物输送体系，并提出了交替共聚药物聚合物作为一种新颖的药物输送载体的设计。通过这些工作的展开，我们发展了几种两亲性大分子药物输送体系和诊断一体化的纳米粒子药物输送体系。本研究为构筑新颖的药物输送体系提供了重要的理论参考和技术支持。在本项目的资助下已经在Polymer Chemistry, Biomaterials Science, Theranostics等国际刊物发表SCI 论文3篇。在项目执行期间，协助培养博士研究生4人。