基于功能化金属-有机骨架纳米杂化材料的生物传感体系的构建及其在癌症早期诊断中的应用

The concentration of tumor markers in living body could reflect the genesis and progression of tumor, thus the development of simple, rapid and accurate detection methods of tumor markers are significant in early diagnosis of cancer. Nanomaterials-MOFs hybrids (NM-MOFs hybrids) not only have the characteristics of MOFs materials including structural diversity, porosity, high specific surface area and chemical stability, but also combine the advantages of nanomaterials (nanoparticles, nanosheets and their nanocomposite),including excellent optical, electrical properties and easy modification, thus NM-MOFs hybrids hold great potential application in biosensing field. In this project,NM-MOFs hybrids with good optical, electrical and magnetic properties were designed and synthesized, novel, high-efficient bio-functionalization strategies were explored to achieve the objective performance of materials.The interaction mechanism of functional molecules with NM-MOFs hybrids were researched and the assembly of functional molecules were regulated. Electrochemical, electrochemiluminescence, fluorescence, colorimetric and strip biosensing system based on functionalized NM-MOFs hybrids were constructed, and their optical, electrical sensing mechanism were explored. Ultrasensitive, highly selectivity, fast and accurate, economical and practical analytical methods for single detection and combined detection of tumor markers were established, which provided theoretical basis for early diagnosis, therapy of cancer and anticarcinogen screening.

肿瘤标志物在体内的含量反映肿瘤发生和发展，开发简单、快速、准确的肿瘤标志物检测方法对于实现癌症早期诊断具有重要意义。MOFs纳米杂化材料（Nanomaterials-MOFs，NM-MOFs hybrids）兼具MOFs材料的结构多样性、多孔性、高比表面积、化学稳定性和纳米材料（纳米粒子、纳米片、纳米复合材料）优良的光、电性质及易于修饰性，因此在生物传感领域极具应用潜力。本项目拟设计合成具有光、电、磁等特定性能的NM-MOFs杂化材料，探索新颖、高效的生物功能化策略实现材料目标性能。研究功能分子与NM-MOFs杂化材料的作用机制，调控功能分子的组装，构建基于功能化NM-MOFs杂化材料的电化学、电化学发光、荧光、比色、试纸条生物传感体系，并探究其光、电传感机理。建立超灵敏、高选择性、快速准确、经济实用的肿瘤标志物的单项检测和联合检测方法，为癌症的早期诊断、治疗和抗癌药物的筛选提供理论依据。

肿瘤标志物与癌症的发展过程密切相关，开发超灵敏、高选择性、快速准确的肿瘤标志物检测方法，对于实现癌症早期诊断和针对高危人群的癌症筛查具有重要价值。本项目构建了基于功能化金属-有机骨架纳米杂化材料（NM-MOFs）的生物传感体系并用于癌症早期诊断研究，主要研究内容、重要结果及科学意义如下：（一）基于ZIF-8、UiO66-NH2、NH2-MIL-88(Fe)和MIL-141(Fe)等金属-有机骨架材料（MOFs），耦合石墨烯、金纳米簇等纳米材料和DNA、染料等功能分子合成了具有分子识别和信号输出能力的功能化NM-MOFs，优化了功能分子的组装并阐明了作用机制；（二）利用功能化NM-MOFs等纳米材料的新型分子识别体系，将其作为负载基质、信号探针或催化剂，进一步结合多种核酸信号放大策略，构建了不同类型的生物传感平台实现了复杂生物基质中癌胚抗原、microRNA、γ干扰素、双氧水等肿瘤标志物的快速、超灵敏和高特异性检测；（三）通过对功能分子与材料构效关系的探索和生物传感体系的光、电传感机理研究，为新型生物传感界面的构建提供了新思路，在癌症早期诊断和药物筛选领域具有潜在的应用前景。相关研究成果在Analytical Chemistry、Chemical Communications、ACS Applied Materials & Interfaces和Journal of Hazardous Materials等学术期刊上发表论文16篇，其中自然指数期刊论文8篇；获授权发明专利1项；培养了1名博士研究生及5名硕士研究生；较好地完成了项目计划书中原定的研究计划和研究任务。