基于超分辨光学成像技术的单颗粒纳米酶催化单分子研究

Nanozyme, a kind of nanomaterial with enzyme-like catalytic activity, has been widely used and becomes one of the hotspots of interdisciplinary research. However, its catalytic mechanism is not yet clear. The basic reason is that the molecular profiling tools for nanozyme catalytic mechanism are still lacking. Due to the heterophase property of nanozyme catalysis, the traditional ensemble-averaging method cannot provide accurate correlation information between the catalytic activity and its microstructure, and is unable to obtain the catalytic characteristics of the single nanozyme, so it is difficult to understand the catalytic essence of the nanozyme. In view of the challenge in the understanding of catalytic mechanism of nanozyme, this project aims to develop super-resolution optical microscopy-integrated single nanoparticle and single molecule optical imaging technology for the study of nanozyme catalysis. Armed with the above analysis platform, we will acquire the real time, in situ and dynamic catalytic information, and establish the direct relationship between the nanozyme catalysis and its microstructural properties (such as geometrical shape, chemical composition, crystalline type, etc). We will further explore the spatial distribution of catalytic active sites and dynamic change on the sub-particle of a nanozyme. Under these investigations, it is expected to reveal catalysis difference of the individual nanozyme, and clarify the nanozyme catalytic mechanism at the molecular level, so as to provide the foundation for rational design and activity regulation of nanozymes.

纳米酶——一类具有类酶催化活性的功能纳米材料，近年来已成为多学科交叉研究热点，但其催化机制尚不明确。究其根本原因，传统整体平均法很难准确得到纳米酶催化与其微观结构相关性信息，更无法获取单颗粒纳米酶的催化特性，而目前适用于纳米酶催化机制研究的分子水平表征工具仍有欠缺，因此难以深入了解纳米酶催化本质。本项目针对纳米酶催化机制认识不足的关键问题以及分子水平研究手段欠缺的技术需求，拟结合团队在纳米酶、单分子检测和光学成像等领域的技术积累，发展基于超分辨光学显微成像的单颗粒纳米酶催化单分子分析技术，建立纳米酶催化光学成像理论和方法，获取单颗粒纳米酶催化的实时、原位和动态信息，建立纳米酶催化与其微观结构基础（如形貌、组分、晶面类型等）的相关性，深入了解纳米酶亚颗粒催化活性位点分布和动态变化特征，从而揭示纳米酶催化的个体差异，阐明纳米酶分子水平催化机制，为纳米酶理性设计及其活性调控提供基础和依据。

本项目围绕单颗粒单分子表征工具的需求，针对纳米酶催化机制问题，系统探讨了新型纳米酶的合成、单颗粒单分子表征技术和仪器系统、光学调控纳米催化特性以及纳米酶治疗应用等相关方面，并取得显著成效：1）结合超分辨成像系统，搭建了纳米酶单颗粒单分子超分辨成像分析平台，实现了实时高分辨率成像分析，构建出适用于单颗粒纳米酶催化研究的超分辨光学成像分析系统；2）基于纳米酶单颗粒催化研究对时间分辨信息获取的需求，发展了单颗粒单分子表征新工具，探索单分子时间分辨表征新方法，并进一步研制新型的纳米间隙电极探针器件，发展基于量子隧穿器件的单颗粒单分子表征技术；3）探索纳米酶催化行为评价与优化合成方法，研究核酸编码调控纳米酶探针合成策略，开展基于纳米酶的特色医学诊疗应用。相关研究成果发表了系列高质量期刊论文，期刊包括《Science Advances》、《Nature Communications》、《Nano Today》、《Science Bulletin》、《Chemical Communications》（封面）、《Particle & Particle Systems Characterization》（封面），受到了跨学科研究领域的广泛关注。