可还原降解的聚合物纳米凝胶用作抗肿瘤药物载体的研究

项目名称： 可还原降解的聚合物纳米凝胶用作抗肿瘤药物载体的研究

项目编号： No.51473037

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 一般工业技术

项目作者： 杨武利

作者单位： 复旦大学

项目金额： 85万元

中文摘要： 环境响应性纳米粒子由于其物理化学性质可随外界的特定刺激发生变化，可用于实现药物在特定的场所、时间及剂量的控制释放。由于二硫键能够在细胞外的氧化环境中稳定存在，而在还原性的肿瘤组织或细胞内环境中被谷胱甘肽还原而发生断裂，因此含二硫键的纳米粒子具有还原响应性，特别适合用作抗肿瘤药物载体。近来，人们发现二硒键也具有氧化/还原敏感性。我们提出系统研究可还原降解的聚合物纳米凝胶在抗肿瘤药物载体方面的应用；系统制备二硫键/二硒键交联的聚合物纳米凝胶并研究其降解过程，基于部分二硫键预还原生成的自由巯基与马来酰亚胺基的反应，实现纳米凝胶的表面功能化，从而获得具有多功能(还原降解和肿瘤靶向)的抗肿瘤药物载体；研究可还原降解的载药纳米凝胶对肿瘤细胞的杀伤作用，发展具有应用前景的抗肿瘤纳米凝胶载药系统。

中文关键词： 纳米粒子；还原响应；生物降解；药物载体；抗肿瘤药物

英文摘要： The environment-responsive nanoparticles could change their physicochemical properties with specific stimuli, and deliver a drug in spatial-, temporal- and dosage-controlled fashions. Normal extracellular matrices possess a low reducing power and are rich in stabilizing disulfides. In contrast, tumor tissues and cytosol have a high redox potential with high GSH concentration, and could cleave the disulfide linkage, thus the nanoparticles with disulfide bond have redox-responsive and are potential anti-cancer drug delivery carriers. Recently, a few researchers have demonstrated that diselenide bonds also have redox responsive behaviors. Here we propose a project to investigate the redox-responsive biodegradable polymer nanogels for anti-cancer drug delivery system systematically. We will prepare series disulfide/diselenide crosslinked polymer nanogels and demonstrate the redox-sensitive degradable process. When part of the disulfide linkage is reductive, a few free thiols would generate on the surface of disulfide crosslinked polymer nanogel and could react with the some target molecules containing maleimide group, when tumor targeted molecules is used, all-in-one drug delivery system (reductive degradation and tumor targeting) would be obtained. In addition, we will study the cytotoxicity of redox-sensitive degradable polymer nanogels to tumor cells, exploring potential nanoparticles used as anticancer drug delivery system.

英文关键词： Nanopartucle;redox-responsive;biodegradable;drug carriers;anti-tumor drug