新型和厚朴酚高分子-PEG键合物的制备及其体内外抗肿瘤研究

项目名称： 新型和厚朴酚高分子-PEG键合物的制备及其体内外抗肿瘤研究

项目编号： No.51203134

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 有机高分子材料学科

项目作者： 梁媛媛

作者单位： 杭州师范大学

项目金额： 25万元

中文摘要： 和厚朴酚（Honokiol,HK）具有强的抗肿瘤活性且能协同增强其他化疗药物的药效，但难溶于水，生物利用度低，限制了其在临床应用。本研究拟设计制备一种新型的两亲性和厚朴酚高分子-PEG键合物(PHK-PEG),其亲水部分由聚乙二醇(PEG)构成，疏水部分由HK与含有缩酮基团的三乙二醇二乙烯基醚单体通过缩合共聚制备的HK高分子（PHK）构成，可具有稳定的高载药量；PHK-PEG在水溶液中可自组装形成纳米胶束，被肿瘤细胞摄取后，可特异地在酸性溶酶体环境内水解并释放游离的HK。本项目拟系统研究PHK-PEG在水溶液的缔合行为、体外药物释放规律、体内药物代谢动力学，以及体内外抗肿瘤活性，探寻其结构与性能之间的相互关系，继而获得该类纳米药物结构与性能的调控方法，并从中优选出高性能的PHK-PEG作为药物载体用于化疗药物阿霉素的负载，以期通过药物间的协同作用，用于耐药肿瘤的治疗。

中文关键词： 和厚朴酚；前药；药物载体；抗肿瘤；

英文摘要： Honokiol (HK) has showed potent anticancer activity and synergistic anticancer effect with other anticancer agent, but its water-insolubility makes its low bioavailability. Herein, we will design a novel type of polymer drug conjugates PHK-PEG- - the high molecular weight honokiol polymers (polyhonokiol,PHK) conjugated with two polyethylene glycol(PEG)chains via acetal bonds that can easily hydrolyze at acidic pH. PHK can be made by condensation polymerization of HK with divinyl ether comonomers contains acetal bonds.In aqueous conditon，PHK-PEG can form stable micelle and serves two roles - as an anticancer prodrug and a drug carrier. As an anticancer prodrug, PHK-PEG micelle will have a high and fixed HK-loading content, and released active HK in the intracellular acidic lysosomes environment. As drug carriers, PHK-PEG micell could carry other anticancer drugs, such as doxorubicin, and ship them into drug-resistant cells, greatly enhancing the cytotoxicity of the loaded drug. PHK-PEG will be a promising prototype that merits further study for cancer therapy. In this work, Following behaviors of PHK-PEG including the self-assembly behavior in water, in vitro and in vivo drug release properties，anticancer effects in vitro and in vivo will be carefully investigated, thus led to the establishment of a structure-act

英文关键词： Honokiol；prodrug；drug carrier；anti-cancer；