项目名称： 铁蛋白-多金团簇复合纳米材料模拟抗氧化酶系的研究

项目编号： No.31500814

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 袁嫕

作者单位： 国家纳米科学中心

项目金额： 20万元

中文摘要： 自由基氧化损伤和天然抗氧化剂的健康作用越来越受到人们的关注。天然抗氧化酶类的生产纯化成本高、半衰期短、体外稳定性较差的劣势限制了其实际应用。以纳米材料为基础的模拟抗氧化酶在清除活性氧自由基、抗炎症反应、促进细胞生长、以及抗衰老方面具有重要的科学意义和广泛的应用前景。本课题创新性的提出以天然生物蛋白酶铁蛋白为蛋白骨架设计多酶联和体系，拟在已有的研究成果基础上，进一步利用基因工程和蛋白质工程的方法改良蛋白骨架，在铁蛋白内部空腔中合成粒径可控、数目可调、具有良好电子传递性能、催化活性位点充分暴露的多金纳米团簇，以获得长效、无毒和高效的抗氧化模拟酶纳米材料，系统研究其对细胞抗氧化应激反应、减少其氧化损伤的治疗效果的构效关系，并阐明其分子作用机制，实现新型多重催化活性的模拟抗氧化酶系统纳米材料的最佳效果，为临床抗氧化、抗炎性和抗衰老相关疾病的药物研发提供新思路。

中文关键词： 自由基；抗氧化；笼状蛋白；纳米模拟酶；构效关系

英文摘要： Overproduction of free radicals can cause oxidative damage to biomolecules, eventually leading to many chronic diseases. Natural antioxidant enzymes, which are responsible for removal of free radicals have short half-life and poor stability in vitro. And there is the cost of their production and subsequent purification to consider. These limitations highlight the need for the continual development of more efficient antioxidant enzyme mimics. Nanoparticles as antioxidant enzyme mimics, with their ability to decrease the numbers of free radicals, would show significant advancements and broad application prospect due to the anti-inflammatory, anti-aging effects and cell growth promotion. In this study, based on methods combining with gene and protein engineering to modify protein template (ferritin), we develop a novel nanosystem with multiple gold nanoclusters at ferroxidase active sites of ferritin, in which the gold nanoclusters will have controllable size and number, excellent conductivity and fully exposed catalytic site in the internal cavity of ferritin. This nanosystem will provide a long-acting, non-toxic and efficient antioxidant enzyme mimic. We also explore the molecular mechanisms of cellular response to oxidative stress and the therapeutic efficacy of reducing oxidative damage. This study, therefore, has significant implications in understanding the interactions of nanostructures with biological systems and assisting in the development of clinical drug design for anti-oxidative, anti-inflammatory and anti-aging diseases.

英文关键词： ROS;antioxidation;cage shaped protein;nanoenzyme mimic;structure-activity relationship