铁基MOFs纳米酶的制备及其在生物传感中的应用研究

Due to the inherent unique characteristics, nanozymes have been widely employed in various fields, such as biosensors and therapeutics. Nevertheless, owing to the inferior catalytic activity and substrate selectivity of nanozymes to protein-based native enzymes, the synthesis of nanozymes with higher activity and specificity is vital. In this work, iron-based metal organic frameworks (Fe-MOFs) nanomaterials were utilized as enzyme mimics. The effect of size and morphology of the proposed nanozymes on their catalytic performance would be investigated systematically by screening and performance control, to reveal the regulating characteristics and common regularity. Furthermore, the elaborate control upon the synthesis of Fe-MOFs nanozymes would be achieved through excavating the catalysis mechanism. In addition, the intrinsic catalysis of these proposed nanozymes and their activity adjustment by nucleic acids would pave the way for the establishment of biosensors for bioactive molecules, for example, nucleic acids and nucleases, in living cells. Besides, the hybrid nanozymes comprising Fe-MOFs and other nanozymes could be further constructed. The exploration of their processing methods and regulating characteristics, as well as the revelation of enzyme-like catalytic mechanism and synergistic catalysis enhancement, would be conducive to the fabrication of versatile biosensors with high efficiency catalysis and biological detection.

纳米酶以其自身独特的性质被广泛应用于生物传感、疾病诊断等诸多领域。然而，在酶的催化活性与底物特异性上，纳米酶与天然的蛋白酶之间仍存在着较大差距。因此，制备具有高催化活性与高底物选择性的纳米酶仍是该领域研究的热点。本项目拟使用铁基金属有机骨架（Fe-MOFs）纳米材料作为模拟酶，通过纳米酶的筛选及性能调控等方法，系统研究其模拟酶催化性能与材料尺寸及形貌的关系，发掘调控及共性规律，阐明催化机理，实现高催化活性与高底物选择性Fe-MOFs纳米酶的可控制备；结合Fe-MOFs纳米酶本身的催化活性，利用核酸对纳米酶活性的调控功能，构建活细胞中核酸、核酸酶等生物活性分子的传感体系。此外，引入其他纳米酶，与Fe-MOFs纳米酶结合，制备多功能的复合纳米酶体系，研究构建方法及调控规律，探索复合纳米酶的类酶催化机制，以及协同增强的催化效应，发展具有高效催化、生物检测等特性的多功能生物传感器。

纳米酶以其自身独特的性质被应用于生物传感、疾病诊断等诸多领域。然而，就催化活性而言，纳米酶与天然的蛋白酶之间仍存在着较大差距。为此，本项目致力于高催化活性纳米酶的开发，合成出不同结构与组成的铁基纳米材料，系统研究了其纳米酶活性，并成功的将他们应用于实际样品中H2O2、核酸酶、葡萄糖及抗氧化剂的分析中。其中，高活性纳米酶开发采取的方法：（1）寻找新型纳米材料作为纳米酶，通过煅烧硫粉与Fe3O4纳米粒子的混合物制备了FeS2纳米粒子。相比于普通的FeS2材料，纳米尺寸的FeS2材料具有更强的过氧化物酶活性。（2）将二维结构的碳纳米片引入材料中制备纳米复合材料，合成了FeP@C、FeS@C与FeS2@C纳米复合材料。研究结果显示，二维结构的FeP@C、FeS@C与FeS2@C纳米酶的催化性能分别明显强于FeP、FeS及FeS2纳米材料的酶活性。（3）利用核酸修饰提高纳米酶的活性，使用长的ssDNA修饰铁基金属有机骨架材料MIL-53(Fe)纳米酶，修饰后的MIL-53(Fe)具有更强的过氧化物酶活性。（4）构建集成式纳米酶MIL-101(Fe)@GOx，利用“纳米邻近效应”提高纳米酶的催化效率。其中，前两种方法是通过提高纳米酶的比表面积，增加纳米酶与底物的接触面积，实现纳米酶活性的升高。而后两种方法则是通过修饰提高与纳米酶接触的反应底物的浓度，提高纳米酶与底物间的传质速率来提高纳米酶的催化效率。最终，利用H2O2、核酸、抗氧化剂对纳米酶活性的调节功能设计了检测H2O2、核酸酶、葡萄糖与抗氧化剂的传感平台。上述研究结果为高催化活性的新型纳米酶的开发提供了参考依据。