Single-Atom Nanozymes: From Precisely Engineering to Extensive Applications

Conspectus Nanozymes are nanomaterials with intrinsic enzyme-like properties that can overcome the current limitations of natural enzymes, such as high preparation cost, instability, restricted application scenarios, etc. Since the Fe₃O₄ nanoparticles (NPs) were shown to possess the peroxidase (POD)-like activity in 2007, thousands of nanomaterials were reported to mimic the catalytic properties of various types of enzymes including catalase (CAT), haloperoxidase, superoxide dismutase (SOD), glucose oxidase, glutathione peroxidase, hydrolase, nuclease, nitroreductase, and others. Particularly, some nanozymes showed multienzyme-like activities with regarding to the changes in application scenarios such as temperature, pH, etc. Benefiting from their distinct physical-chemical characteristics and enzyme-like catalytic properties, the nanozymes have been widely applied in various biomedical related fields from in vitro detections to in vivo therapeutic treatments. However, currently their ambiguous structure-function correlations and relatively inferior activities compared to natural enzymes promote extensive efforts for the modifications on current nanozymes and development of novel alternative nanozymes. The single-atom nanozymes (SAzymes) present a unique way to mimic the highly evolved enzyme active centers, because of their atomically dispersed catalytic sites, which leads to high atom utilization efficiency and, thus, potentially extraordinary catalytic activity. Also, the abilities to modify the active centers and/or tune the interactions between the metal centers and supporting ligands provide a precise way to engineer the SAzymes at atomic levels. Given their well-defined geometric and electronic structures, the SAzymes thus can serve as exceptional templates for deciphering the structure-function relationships, which is beneficial for further improving their catalytic performances. In this Account, we will review our recent efforts and other notable works on the developments of SAzymes as effective enzyme mimics and their applications in the biomedical related areas. We will begin with a brief introduction for nanozymes and why the emergence of SAzymes, as a novel artificial enzyme, tackles some of the challenges nanozymes are facing. Next, we will focus on the systematic design, synthesis and optimization of SAzymes, especially on the impacts of engineering the metal centers and their ligands environment on their activities from an enzymologist perspective. For example, with alternations of first-shell ligand from N to P/S, the SAzymes’ CAT-like activity were increased more than 4-fold. The changes in the coordination numbers (x) for Co-N_x(C) SAzyme significantly altered its oxidase (OXD)-like kinetics and catalytic activity. Then, we will discuss the ways for the standardization of SAzymes’ specific activity and enzyme-like kinetics. We will also review the wide ranges of their applications from colorimetric detections of biologicals, antibiosis treatments, to cancer therapies. Finally, we will address the current challenges and future perspectives the SAzymes are facing.