MnGA with multiple enzyme-like properties for acute wound healing by reducing oxidative stress and modulating signaling pathways.

Nanozymes with specific catalytic activity inhibit inflammation and promote wound healing efficiently and safely. In this work, multifunctional manganese-based nanozymes (MnGA) with antioxidant properties were successfully constructed via a simple coordination reaction in which manganese chloride was used as the manganese source and gallic acid (GA) was used as the ligand solution. MnGA possesses both catalase-like (CAT-like) and superoxide dismutase-like (SOD-like) activities and a reactive nitrogen species (RNS) scavenging capacity, which enables it to efficiently inhibit the inflammatory response. Specifically, MnGA scavenges superoxide anions and produces HO via SOD-like activity and then consumes HO to convert it to nontoxic HO and O via CAT-like activity, resulting in a cascade of catalytic reactions to scavenge reactive oxygen species (ROS). Moreover, the scavenging of RNS by MnGA can amplify the anti-inflammatory effect in combination with the scavenging of ROS. RNA sequencing of mouse skin tissue further revealed that MnGA significantly reduces inflammation by modulating the nuclear factor kappa-B (NF-κB), Toll-like receptor (TLR), and NOD-like receptor (NLR) signaling pathways and promotes skin regeneration. In summary, MnGA nanocatalysts possess excellent antioxidative and anti-inflammatory properties, highlighting their potential applications in wound healing and inflammation treatment.