基于超分子自组装的可示踪纳米粒子共载基因与化疗药物用于癌症治疗的研究

项目名称： 基于超分子自组装的可示踪纳米粒子共载基因与化疗药物用于癌症治疗的研究

项目编号： No.21303145

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： 吴云龙

作者单位： 厦门大学

项目金额： 25万元

中文摘要： 药物耐药性是导致肿瘤化疗失败的重要原因，研究克服耐药的有效新途径、提高患者存活率是当前肿瘤治疗中迫切需要解决的课题。最近研究表明，新型药物传递系统共载基因与化疗药物进行联合治疗具有良好的协同增效作用，然而该方法对于药物载体的设计提出了更高的要求。前期研究中，我们发现基于环糊精的超分子结构由于其良好的生物相容性和分子识别自组装能力使其在药物载体的设计上拥有独特的优势。在本项目中，我们将利用已获得的高效低毒环糊精阳离子衍生物结合可发光的量子点组装为多功能药物载体；选择可与环糊精形成主客体复合物的紫杉醇作为模型化疗药物，评价其药物装载能力；针对耐药癌细胞中高表达的Bcl-2蛋白，利用可逆转其抗凋亡功能的Nur77作为模型基因；研究该新型载体的基因/化疗药物共载能力，同时考察其示踪功能及安全性；探索超分子自组装纳米粒子共载基因/化疗药物协同增强肿瘤治疗效果的新方法。

中文关键词： 环糊精；超分子自组装；纳米粒子；癌症治疗；基因/药物共载

英文摘要： Multi-drug resistance (MDR) is an important reason leading to failure of chemotherapy. Currently, novel and effective approach to overcome MDR and improve patient survival rate are crucial issues in cancer therapy. Recent studies have shown that the novel drug delivery system (DDS) with the capacity to co-deliver gene and chemotherapy drug exhibited enhanced therapeutic effects. However, this approach requires design of novel drug carriers with higher complexity. In preliminary studies, we have demonstrated that the cyclodextrin-based supramolecular structures could be utilized as novel drug carriers due to their good biocompatibility and drug loading ability by specific molecular recognition and self-assembly. In this project, we propose to use our cationic derivatives of cyclodextrin, with low toxicity and high drug delivery efficiency, and trackable quantum dots for the synthesis of multi-functional drug carrier; after that, we choose paclitaxel with the ability to form specific host-guest inclusion complex with cyclodextrin as model drug to test the drug loading ability of this novel supramolecular carrier; considering the high expression of Bcl-2 protein in drug-resistant cancer cells, we will utilize Nur77 as a model gene with the ability to reverse the anti-apoptotic function of Bcl-2 protein; moreover, c

英文关键词： Cyclodextrin；Supramolecular Self-assembly；Nanoparticle；Cancer Therapy；Gene/Drug Co-delivery