多肽自组装的设计及其对抗癌药物的控制释放研究

项目名称： 多肽自组装的设计及其对抗癌药物的控制释放研究

项目编号： No.21276285

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 化学工业

项目作者： 刘又年

作者单位： 中南大学

项目金额： 80万元

中文摘要： 针对目前临床使用的常规化疗药物普遍存在剂量大、药效低、毒副作用高的缺点，本项目拟设计多功能的多肽分子，通过自组装的方式对药物进行包覆，制成纳米药物，使其具有靶向性和控制释放的特性。主要内容主要包括：(1)设计能形成β-折叠的多肽序列，通过与药物自组装实现药物的包覆；(2)研究多肽与药物自组装的机理；(3)从分子层面探讨多肽分子结构与纳米药物药效之间的关系。项目的创新点：其一是在多肽中引入非天然氨基酸，以改善多肽链的柔性及抗酶解能力；其次是引入树枝状氨基酸、含巯基的氨基酸和pH敏感的氨基酸序列，实现多肽对药物的有效包覆和控制释放。这种多功能多肽自组装包覆的抗癌药物，易克服生理屏障，进入肿瘤细胞内部，并借助多功能多肽对肿瘤环境的敏感特性调控药物释放，以期在解决如何提高抗癌药物的药效、降低毒副作用等问题和关键技术上取得突破，为高效抗癌药物的研发提供相关科学依据。

中文关键词： 纳米药物载体；抗肿瘤药物；分子自组装；可控释放；分子识别

英文摘要： Efficient treatment of cancer is of crucial importance. However, many anticancer drugs are required for high dose leading to less effective and serious side effects.In this project, we aim to design multifunctional peptides,which not only load anticancer drugs through self-assembly, but also target and controlled release the loaded drugs on cancer cells/tissues. The main work in this project includes: (1) Design and synthesize of peptides which consist of β-sheet segment, and then drug loading via self-assembly of pepetides and drugs; (2) Finding out the mechanism of self-assembly of peptide with drugs; (3) Getting insight into the relationship between the activity of loaded drugs and the structure of the assembling peptide. The innovation of the project includes: firstly, the introduction of unnatural amino acids improve the flexibility and the resistance to enzymatic hydrolysis of the peptide; secondly, to achieve high loading and controlled release of the drugs, dendritic, thiol, and pH-sensitive amino acids are employed; thirdly, a targeting ligand specifically binding to cancer cell is also attached to the backbone of the peptide. Overall, in this project, we are trying to provide a novel strategy to improve the chemotherapeutic efficacy of the anticancer drugs. This kind of anticancer drug delivery system

英文关键词： nanocarrier；anticancer drug；self-assembly；control release；molecular recognition