Rational Design of Single-Atom Nanozymes for Biomedical Applications

Introduction: Natural enzymes play crucial roles in various biomedical fields, particularly in biosensing. Nevertheless, their use is often limited by high costs and limited stability. Therefore, there is an urgent need to develop artificial alternatives with enzyme-like properties and enhanced stability for low-cost biomedical applications. Nanozymes have emerged as a promising alternative to natural enzymes, offering advantages such as mimicking enzymatic functions, high catalytic stability, easy modification, and low fabrication costs. These attributes make nanozymes highly suitable for use in biosensors to amplify signals and improve detection performance. Precisely designing single-atom nanozymes (SANs) at the atomic level to achieve isolated metal active sites can significantly enhance their enzyme-like catalytic activity, thereby boosting their performance in biomedical applications.

Methods: We designed various SANs to mimic the structure of heme-based enzymes' active centres, achieving enzyme-like properties comparable to natural ones. Specifically, Fe-N-C-based SANs are reasonably designed via different strategies, including a secondary-atom-assisted method, MnO_x nanoconfinement, an ion-imprinted approach, and P atom adjustment strategies, etc.

Results: The SANs demonstrated superior robustness compared to natural enzymes, maintaining excellent stability under varying pH levels and temperatures. Their exceptional catalytic specificity for hydrogen peroxide suggests they could effectively replace natural peroxidases in high-sensitivity biosensing. To explore practical applications, we developed electrochemical sensors, immunosorbent assays, intercellular nanoprobes, and lateral-flow immunoassays based on SANs for biosensing and bioimaging.

Conclusions: The developed SANs exhibit excellent enzyme-like activity, selectivity, and stability due to their unique electronic and geometrical properties. These features offer substantial potential for substituting natural enzymes in various biomedical applications. To continuously monitor human health, we further integrated SANs into wearable microgrids. This development aims to meet the demands for autonomous, self-powered, self-regulated, and flexible wearable energy management and sensors, thereby enabling comprehensive healthcare monitoring and advanced human--machine interfacing.