新型水溶性梳状聚合物抗肿瘤药物载体的制备与生物学性能研究

项目名称： 新型水溶性梳状聚合物抗肿瘤药物载体的制备与生物学性能研究

项目编号： No.51503013

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 一般工业技术

项目作者： 喻青松

作者单位： 北京化工大学

项目金额： 22万元

中文摘要： 与传统的线性聚合物相比，树枝状聚合物由于其精确的化学组成和支化结构，在抗肿瘤药物载体应用方面具有极大的优势，但是其复杂的合成与纯化过程极大地限制其应用。与之相比，梳状聚合物具有相似的生物学性能，其合成和纯化过程更为简单，结构与组成调控更加容易，因而拥有广阔的应用前景。本项目旨在基于FDA批准应用于临床研究的聚环氧乙烷（PEO）和聚（（N-2-羟丙基）甲基丙烯酰胺）（PHPMA）等水溶性聚合物构建新型梳状聚合物纳米载药体系，探索上述梳状聚合物的高效合成方法，实现聚合物化学组成与拓扑结构的精确调控。通过先进表征手段研究聚合物的理化性质与生物学性能，分析其与聚合物组成和拓扑结构的内在联系。在此基础上对聚合物组成和结构进行优化，以期获得具有优异的长循环性能、肿瘤靶向能力和肿瘤组织穿透能力的新型抗肿瘤纳米药物载体用于进一步的临床前研究。

中文关键词： 肿瘤化疗；梳状聚合物；聚合物药物偶联物；长循环；肿瘤靶向

英文摘要： Dendritic polymers possess greater advantages over the traditional linear polymers in the field of anticancer drug carriers due to their precisely controlled composition and branching structure. However, because of the complicated synthesis and purification process, their potential application was greatly restricted. In contrast, the comb-like polymers which have comparable biological properties to the dendritic polymers can be more easily fabricated and purified. Besides, their tunable structure and chemical composition offer them broader application prospects. Herein, the aims of this proposal are to construct novel comb-like polymeric anticancer drug delivery systems based on the FDA-approved poly(ethylene glycol) (PEO) and poly((N-2-Hydroxypropyl) methacrylamide) (PHPMA). The efficient synthesis of the polymers will be explored to achieve the precise control of their chemical composition and topological structure. The physic-chemical properties (hydrodynamic size, shape, etc.) and the related biological properties (blood circulatory half-life, biodistribution, etc.) will be characterized by various advanced techniques to analyze the internal relationship between the chemical composition or topological structure and their physic-chemical or biological properties. The polymer composition and structure will be optimized on the basis of these links so that more optimal polymeric drug delivery systems with longer circulatory half-life, better tumor targeting ability and better tumor penetrating properties could be obtained for further preclinical studies.

英文关键词： Cancer chemotherapy;Comb-like copolymers;Polymer-drug conjugates;Long circulating;Tumor targeting