Ligand-TargetedAg₉ Cluster Self-CascadeAntioxidants for Enhanced Reactive Oxygen Species Clearance in theTreatment of Inflammatory Bowel Disease

Atomically precise metal nanoclusters (MNCs) with flexible peripheral ligands provide selective channels and unique electronic structures to the rigid metal core, showing great application potential in many fields such as biomimetic nanozymes. In this study, we developed cost-effective, low-toxicity, and water-soluble MNC based self-cascade antioxidants for enhanced reactive oxygen species clearance. Compared to Ag nanoparticles, the Ag₉ NCs with a monovalent Ag core coordinated by nonmetallic S and O show superior superoxide dismutase-like (inhibition 86.7%) and catalase-like (<i>K</i>_m = 20.37 mM, <i>V</i>_max = 3.13 × 10^–3 mM s^–1) activities. Interestingly, the −COOH groups on the ligands endow Ag₉ NCs with a −42.5 mV negative surface charge, enhancing the targeting to inflammatory cells. Additionally, Ag₉ NCs’ remarkable therapeutic effects have been confirmed in cell cultures and an inflammatory bowel disease (IBD) model. Thus, this study proposes a novel cluster-based nanozyme that utilizes ligands for targeting and monovalent metal cores for catalysis, demonstrating significant therapeutic potential for IBD treatment.