碳点对蛋白纤维化调控作用及其机制热力学基础

At the beginning of the 20th century, Alzheimer's disease was discovered for the first time, and it began to get attention from 1980s. At present, scientists remain committed to the clinical treatment of this disease. More and more nanoparticles have demonstrated excellent performance in the fields of biomedical imaging and labeling in recent years, and their applications in the filled of protein fibrillation have aroused researchers’ interests gradually. Carbon dots is a kind of nanomaterials with good biocompatibility. In this project, a series of low toxic carbon dots with different size, component, structure, surface modification etc. will be designed and synthesized. By the use of isothermal titration calorimetry (ITC), fluorescence spectrometer, circular dichroism, dynamic light scanning, microanalysis etc., the interactions between carbon dots and protein will be carefully studied at the macromolecular level to obtain thermodynamic and kinetic parameters of the process. The kind of interaction and the mechanism will be found after analyzing the thermodynamic and kinetic parameters, and the target site can be demonstrated by molecular dynamics simulation. The surface, compose, size and structure of carbon nanomaterials can be modified by chemical method to realize different regulation for fibrillation, such as promotion, inhibition or depolymerization by analyzing the kind of interactions and the mechanisms. Taking all of the results into consideration and summarizing the relationship between regulating mechanism and the compose of carbon nanodots. This work will provide theoretical basis for the application of nanomaterials in the treatment of neurodegenerative diseases, and further providing scientific basis for high efficiency and safety use in biomedicine.

上世纪80年代以来，阿尔兹海默症越来越引起人们的关注，研究表明其与蛋白纤维化密切相关。近年来纳米材料对蛋白纤维化的影响引起了关注，但作用机制尚未阐明。碳点是一类生物相容性很好的纳米材料。本项目拟设计并合成一系列不同组成、结构、尺寸、表面性质的低毒碳点，利用等温滴定量热、荧光光谱、圆二色谱、显微分析等，研究蛋白纤维化过程及碳点对其调控作用机制，获取相关过程的热力学和动力学信息；通过对相关参数的分析，得到作用力类型及作用机制；结合分子动力学模拟，诠释靶向作用位点、作用方式及其作用热力学信息；针对作用力类型、作用机制、靶向作用位点及其作用方式，对碳点的组成、结构、表面性质进一步优化改性，实现对蛋白纤维化行为精确调控（促进、抑制、解聚）。归纳总结碳点组成、结构与蛋白纤维化调控作用的关系。将为纳米材料在神经退行性疾病治疗中应用提供理论基础，也为其进一步在生物医学中高效、安全的应用提供科学依据。

上世纪80年代以来，阿尔兹海默症越来越引起人们的关注，研究表明其与蛋白纤维化密切相关。近年来，纳米材料对蛋白纤维化的影响引起了关注，但其作用机制尚未阐明。碳点是一类生物相容性很好的、水溶性的纳米材料。本项目设计并合成了一系列不同组成、结构、尺寸、表面性质的低毒碳点，利用等温滴定量热、荧光光谱、圆二色谱、显微分析等，结合分子动力学模拟，研究了蛋白纤维化过程；进行了多角度的综合探索，从热力学和动力学出发，系统诠释了不同碳点对蛋白纤维化调控作用，实现了对蛋白纤维化行为精确调控；全面归纳总结了碳点组成、结构、表面性质与蛋白纤维化调控作用的关系。通过整合所获取的热力学和动力学信息，构建了碳点的“构-效”关系模型，揭示了碳点对蛋白纤维化调控的作用机理，诠释了碳点对蛋白纤维化调控作用规律。该项目实现了集“靶向”、“高抑制活性”、“示踪”等功能于一体，完成了“单颗粒多功能”的设计理念，为设计出具有更高抑制蛋白纤维化活性和更好选择性的碳点，提供了理论基础。.项目21873075的相关研究工作共发表了SCI论文22篇（其中一区7篇、二区4篇），于2019年获湖北省自然科学奖三等奖，刘义于2019年获国家百千万人才工程国家级人选，并授予“国家有突出贡献中青年专家”称号，很好的完成了项目研究任务。