External Stimuli-Activable Single-Atom Nanozymes for Bioapplications

Single-atom nanozymes (SANs) emerge as promising alternatives to natural enzymes by precisely dispersing and controlling metal active sites at the atomic level, thereby maximizing catalytic site exposure and mimicking enzyme-like structures. Recently, strategies that integrate SANs with external stimuli to enhance catalytic efficiency or selectively trigger activation are attracting increasing attention in various biomedical fields. However, the underlying mechanisms of the performance enhancement of SANs through external stimuli remain unexplored. Here, we discuss the engineering principles and strategies to improve the performance of SANs, with a particular emphasis on stimuli-activable systems. Specifically, we review how external stimuli (such as light, ultrasound, and magnetic fields) can modulate the electronic structure of active sites and the physicochemical properties of supporting materials, thereby enhancing charge transfer, substrate activation, and reactive oxygen species generation. Furthermore, we provide an overview of the latest applications of stimuli-activable SANs in biosensing, cancer therapy, tissue regeneration, and theranostics platforms. Lastly, we provide the prospects, challenges, and opportunities for external-stimuli SANs.