Bioinspired rational design of nanozymes

Abstract

Nanozymes, an emerging class of artificial enzymes, have attracted increasing attention for their potential in environmental monitoring, industrial catalysis, food safety, and biomedicine. To date, more than 1500 nanomaterials have been identified with enzyme-like activities, some demonstrating catalytic performances that match or even exceed those of natural enzymes. Despite this progress, key challenges remain, including poorly understood catalytic mechanisms, ambiguous structure–activity relationships, and a heavy dependence on nonspecific surface sites, all of which limit the efficiency, selectivity, and broader application of nanozymes. To address these limitations, researchers are turning to nature for inspiration, seeking to reconstruct enzyme active centers at the atomic scale and establish innovative design principles. This review examines the catalytic mechanisms and structural characteristics of natural enzymes, integrating machine learning approaches to investigate nanozyme kinetics, transition state stabilization, electron/proton transfer, and cooperative effects. It highlights bioinspired strategies such as three-dimensional structure design, cofactor incorporation, and artificial organelle systems. Furthermore, the review explores rational nanozyme design using activity descriptors and predictive modeling. Finally, it outlines the transformative potential of artificial intelligence and multiscale simulations in optimizing nanozyme performance, offering a theoretical foundation for the development of next-generation intelligent nanozymes.