基于多肽骨架的肿瘤靶向双靶点药物Janus型树枝状化合物的研究

项目名称： 基于多肽骨架的肿瘤靶向双靶点药物Janus型树枝状化合物的研究

项目编号： No.21472130

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 环境科学、安全科学

项目作者： 郭丽

作者单位： 四川大学

项目金额： 70万元

中文摘要： 在课题组长期从事树枝状化合物和靶向药物研究基础上，结合国外目前的研究成果，首次提出运用树枝状化合物设计理念，研究具有精确结构的两亲性Janus型(肿瘤靶向肽片段)m-肽型树枝状载体-(双靶点药物)n分子的研究设想，研究内容是Dendrimers领域的前沿工作。将αvβ3受体识别功能的肿瘤亲和性靶向多肽载体以及TS及DNA Todo Ⅰ双靶点的抗肿瘤治疗药物相偶联，并通过多肽型树枝状载体调节靶向肽与药物的偶联比例，建立方法学，研究空间结构拟球形的蛋白型分子独特的性质、靶向性和生物活性的关系，探明靶向特征、树枝状效应、胶束形成及多米诺骨牌降解等特性。本项目研究的Janus型分子将与传统研究的肿瘤靶向分子完全不同，在靶向性、体内转运、药物缓释等方面具有特殊性质，有助于解决传统设计的弊端并突破现有研究瓶颈，为突破性结构靶向药物的研制创立新思路和新方法。

中文关键词： Janus；型树枝状化合物；肽型树枝状载体；肿瘤靶向肽；双靶点药物；胶束

英文摘要： Based on our previous work about dendrimers and target drug delivery, the latest study from other scholars, and the strategy of dendritic drug system design, we first present to study the novel amphiphilic Janus peptide dendrimers as the model (tumor-targeting peptide)m-dendritic carrier-(dual target drug)n, which are cutting-edge research in dendrimer field. Tumor targeting peptide (based on αvβ3-intergrin ligand) and dual-target anti-tumor drugs (target TS and DNA TodoⅠ) are grafted on dendritic peptide carrier, and the ratio of targeting moieties/ drugs can be controlled by the dendrimer carrier. This project will establish the methodology of the synthesis of this type of dendrimers, study the conformational behavior of the peptide dendrimers as artificial protein. Moreover, the relationship between targeting effect and anti-tumor activity, the dendritic approach, the micelles self-assembled from Janus dendrimers, and the degradation of dendrimers as domino also intersete us. Summarily, the designed dendrimers, which are totally different from conventional tumor targeting drugs, are promissing to exhibit extraordinary properties such as tumor targeting effect, drug delivery and drug release. This project may solve the problems of the shortcoming of current studies, and provide groundbreaking approach for drug delivery system.

英文关键词： Janus Dendrimer;Peptidr dendrimer carrier;tumor targeting peptide;dual-target drug;micelles