多肽改性聚多巴胺纳米材料的生物传感研究及其在阿尔茨海默病分析中的应用

The key to the treatment of major brain diseases is their early diagnosis and intervention, and to develop new technologies for early diagnosing major brain diseases is significant to improve the national health. This project aims to combine the technologies, including controllable preparation of polydopamine nanomaterials (PDA), surface functionalization and assembling, specific molecular recognition and live on-line analysis, for studying biological sensing based on the interaction of peptide and PDA. By integrated the surface functionalized PDA with peptide and its specific molecular recognition process, the novel mechanisms and methods for effect biological fluorescent sensing will be developed to analyze the brain living system of rats’ model with Alzheimer's disease (AD) pathology. The goal of high sensitive and specific detection of AD-associated markers will be realized in such system and body fluids (e.g. cerebrospinal fluid, blood) in view of their concentrations and changes over the course of disease development. In the project, the research will be started from the study of novel principles for PDA’s surface functionalization, new mechanisms for biological sensing and updated assays, and continue to detect sole AD’s biomarker, investigate the interaction between multiple AD’s biomarkers, furthermore, study the disease mechanisms and explore the potential of early disease diagnosis by in vivo analysis, so that a scientific way will be provided to AD’s thorough research and precise medical treatment.

脑重大疾病的早期诊断及干预是脑疾病治疗的关键，发展脑重大疾病早期诊断新技术，对提高国民健康具有重大意义。本项目拟通过将聚多巴胺纳米材料（PDA）可控制备、表面功能化及组装、分子特异性识别和活体在线分析技术等相结合，开展基于多肽—PDA相互作用的生物传感研究；利用多肽作为基元对PDA实现表面功能化并整合多肽特异性分子识别过程，构建高效生物荧光传感新机制、新方法，并用于分析大鼠阿尔兹海默症（AD）病理模型的脑活体系统，实现高灵敏特异性检测AD相关的多种标志物在脑活体系统及体液（如：脑脊液、血液）中的浓度水平和随病程发展的变化规律。项目将从PDA表面改性新策略、生物传感识别新机制、分析新方法研究入手，从与AD相关单一标志物的检测，到多重标志物交互关系的研究，再到通过活体分析研究病理机制和早期诊断的探索，从而为AD的深入研究和精准医疗提供科学的途径。

高性能传感分析复杂样本中的不同生化物质，是人类探索各种自然现象，揭示内在机制的有力工具，对于解决疾病早期诊断、传染病防控、食品安全、环境监测等重大需求而言具有重要意义。在本项目中，我们围绕高性能生化传感分析这一重要方向开展了系统的基础及应用研究，从生物分子功能化聚多巴胺纳米材料、生物配体调控稀土离子天线效应、微环境调控、多肽修饰扩展栅极场效应晶体管等方面开展工作，与模式识别、金属有机配位、时间分辨荧光、电子器件、比色分析等技术联用，发展了一系列高性能生化传感分析新原理新方法，实现对多种重要靶标（如：金属离子、小分子、蛋白等）的分子识别和高性能检测，在阿尔茨海默等相关疾病早期诊断、环境污染物检测等方面得到了广泛的应用。至今，我们已经完成了项目中的各项任务，在Nature Communications、ACS Nano、Analytical Chemistry等专业期刊上发表SCI收录论文25篇，授权发明专利4项，取得了较好的研究和应用成果。