Single-atom nanozymes: a new platform for central nervous system disease research

Featuring complex neural architectures, the central nervous system (CNS) poses a high risk of irreversible damage or chronic diseases upon injury by inflammatory factors. However, due to the existence of the blood-brain barrier (BBB), drugs can hardly penetrate the nervous system, making new therapeutic approaches urgently needed. Recently, single-atom nanozymes (SAzymes) have emerged as a promising platform for a wide range of therapeutic applications, capitalizing on their distinctive features including atomic-level dispersion of active sites, complete atom utilization, and a tunable coordination environment. Compared with traditional nanozymes, SAzymes exhibit superior catalytic activity, more decipherable structure-activity relationships, and greater tunability of their active site properties. Therefore, this review systematically summarizes and provides an in-depth discussion of typical single-atom nanozymes, including carbon materials, metal-organic frameworks (MOFs), metal oxides, and metal sulfides. Leveraging the anti-inflammatory and antibacterial properties, the roles of various SAzymes in brain injury, stroke, neurodegenerative diseases, biological monitoring, and neuroprotection have also been elaborated in recent years. Simultaneously, based on the latest developments in SAzyme research, novel therapeutic strategies for these diseases are further proposed. Finally, we conduct an in-depth analysis of the key challenges and future research directions for SAzymes.