Ultrasmall Cu₂O@His Nanozymes with RONS Scavenging Capability for Anti-inflammatory Therapy

High concentrations of reactive oxygen and nitrogen species (RONS) are key characteristics of inflammatory sites. Scavenging RONS at the site of inflammation is an effective therapeutic strategy. This study introduces ultrasmall Cu₂O@His nanoparticles with RONS-scavenging ability for the treatment of inflammatory bowel disease (IBD) in mice. The strong coordination between the nitrogen atom in histidine (His) and copper enhances the dispersion and stability of Cu₂O@His. Due to their small size and large surface area, Cu₂O@His exhibits outstanding RONS-clearing ability. Importantly, Cu₂O@His can target mitochondrial sites and repair damaged mitochondria. With excellent dispersion and scavenging RONS ability, Cu₂O@His demonstrates good efficacy in treating mouse IBD. This work provides a new paradigm for developing nanozymes with an ultrasmall size and multiple scavenging RONS abilities.