基于金属有机框架纳米酶的构建及性能研究

Nanozymes have received much attention due to the advantages over natural enzymes, such as low costs, high activity, facile production on large scale, and high stability in different environments. Among them, the flexible combination of metal nodes and organic ligands in MOFs offers multiple catalytic sites and thus MOFs are regarded as one of the promising nanozymes for further investigation. However, it is challenging for the application of MOFs-based nanozymes due to the low activity, lack of specificity, and toxicity. To address the disadvantages, we will screen the nano-MOF enzymes to optimize their catalytic activities. In this context, the relationship of activities and metal centers, coordination modes, and bridging motifs of MOFs will be studied extensively. Moreover, nano hybrid of MOF-Au-CeO2 will be fabricated to mimic multiple enzymatic reactions, which will offer opportunities for the investigation of correlation of catalytic activity and stability by the combination of atom simulation. Finally, the catalytic activity in a confined bioenvironment will be studied by microfluidic-based coating the optimal MOFs nanozymes with vesicles or cytomembranes. In-vivo experiments will be carried out on the basis of the above system. We believe that this project is an important step to develop MOFs nanozymes for future biomedical applications.

纳米酶由于具备低成本、稳定、可大批量生产的优点成为重要的仿生酶体系，引起了研究人员的广泛关注与探索。其中，MOFs体系凭借其多活性位点，配位数及配体种类的多样性，在模拟生物酶领域显示出较大的潜力。然而，其活性低、缺乏底物特征结合位点及生物毒性等，使其临床转化面临巨大挑战。本项目中，我们首先选择具备纳米酶所需诸项特点的金属有机框架作为设计纳米酶的主体材料，通过优化筛选得出金属种类、配位数及官能团种类与纳米酶催化活性的关系。然后，利用次级杂化结构的调控，结合实验结果及理论计算，优化设计提升纳米酶活性、稳定性。最后，借助微流控技术实现囊泡或细胞膜的包覆，通过纳米限域进一步提升催化活性的同时降低生物毒性。本项目的研究成果对于纳米酶的优化设计及拓展纳米酶由生物体外向体内的延伸具有重要的指导意义。

生物酶在生命体生理代谢和现代合成工业中具有重要的作用，主要表现在其高效的催化性能方面，可以使反应速率加快107倍。然而，生物酶固有的局限性，如成本高、稳定性差、储存困难等促进了各种仿生酶的出现和发展。无机纳米酶由于具备低成本、稳定、可大批量生产的优点成为重要的仿生酶体系，引起了国内外研究人员的广泛关注与探索，并已经开发了针对恶性肿瘤的基于纳米酶的协同疗法。然而，纳米酶固有的全身毒性、免疫抑制和低治疗效率限制了进一步应用。在此，我们开发了一种兼具生物相容性、多功能性的无机纳米制剂，可同时整合化学动力学、饥饿和光热疗法。这种纳米剂通过芬顿反应有效地将内源性H2O2转化为剧毒的羟基自由基。还可以通过清除细胞内谷胱甘肽和葡萄糖来实现强化的癌症治疗。此外，红细胞膜的包覆可以极大降低巨噬细胞对纳米剂的免疫识别，进而实现了增强的抗肿瘤免疫效应。与传统的无机化学动力学纳米材料相比，该纳米制剂还具有出色的光热效率。综上所述，该生物制剂表现出有效的肿瘤治疗结果，为开发高效协同疗法提供新途径。