以聚酰胺-胺树状大分子为基础的仿蛋白质分子纳米靶向药物研究

项目名称： 以聚酰胺-胺树状大分子为基础的仿蛋白质分子纳米靶向药物研究

项目编号： No.21474085

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 数理科学和化学

项目作者： 陈圣福

作者单位： 浙江大学

项目金额： 88万元

中文摘要： 纳米靶向药物因其优良的治疗效果和广泛的应用前景而备受关注。然而，现有纳米靶向药物和具有专一性识别能力的抗体等蛋白质分子相比仍然存在巨大差距。借助树状大分子的三维结构，通过对蛋白质分子的特征结构模仿和组合，有可能使纳米药物获得类似蛋白质分子的智能调控的专一性靶向能力。因此，本课题提出了以树状大分子为平台，从模仿蛋白质分子表面两性离子特征出发，通过修饰天然蛋白质分子的识别基团和包载小分子药物，以及进一步微调其表面化学组成和结构，实现智能响应能力，提高生物相容性、体内靶向能力和抑瘤能力。这将使仿蛋白质功能分子兼具蛋白质分子的高专一性、高活性、高生物安全性等特点，合成分子的稳定、较廉价、易于大规模生产的优势，使之能够成为未来可用于临床的纳米靶向药物。这对癌症治疗具有重要的学术价值和实际意义，而且也有助于了解蛋白质分子复杂功能与其简单化学结构的多因素协同方式间的关系，揭示蛋白质分子功能的化学本质。

中文关键词： 生物医用高分子；生物相容性；药物控制释放；肿瘤靶向；纳米药物

英文摘要： The investigation of targeted nano drug delivery draws great attention due to its good therapeutic results and promising potential applications. However, polymer based targeted nano drug vehicle is far away from nature protein molecules in terms of biocompatibility, specificity and efficiency. We believe that it is possible for polymer molecules to achieve protein like efficacy through mimicking the features of protein molecules. Thus, we proposed a mimic way to synthesize an artificial protein with advanced functions. The artificial protein will be achieved by surface modification of generation five poly(amido amine) ( G5 PAMAM) dendrimer by zwitterionic groups and targeting groups and encapsulation of anticancer drug. Moreover, the affinity of targeting groups could be tuned up through forming charge attraction between protein mimics and cell membrane in acidic tumor site and be tuned down in blood stream, in which way to improve the targeting efficiency and reduce toxicity to healthy tissues. Meanwhile, the zwitterionic shell will reduce the nonspecific interaction with blood proteins and cells to escape the clearance by reticuloendothelial system. The final artificial protein could have both advantages of protein and synthetic molecules to efficiently inhibit cancer growth and lower toxicity to health tissues at low cost and high stability. This project will also help us understand the mechanism of protein advanced functions from the organization and coordination of simple chemical structure.

英文关键词： Biomedical polymer;biocompatibility;drug controlled release;tumor targeting;nanomedicine