2D Cobalt Oxyhydroxide Nanozymes Inhibit Inflammation by Targeting the NLRP3 Inflammasome

Abstract Nucleotide‐binding domain and leucine rich repeat family pyrin domain containing 3 (NLRP3) inflammasomes are implicated in diverse inflammatory diseases, so their activation needs to be tightly controlled. Over generation of reactive oxygen species (ROS) is a key factor in NLRP3 inflammasome activation. Consequently, nanozymes with ROS scavenging ability are potential inhibitors of NLRP3 activation and promising therapeutic agents for related inflammatory diseases. Herein, a type of 2D cobalt hydroxide oxide nanosheets (Co NSs), a nanozyme with excellent multienzyme‐like activity, possessing peroxidase (POD), catalase (CAT), and superoxide dismutase (SOD) activities, exhibits superior ROS scavenging properties and protects cells from oxidative damage. Density functional theory (DFT) calculations further reveal these enzyme‐like catalytic reactions of ROS eliminating are spontaneous and CAT is dominant under physiological conditions. Performing multienzyme properties, Co NSs present excellent anti‐inflammation activity by blocking NLRP3 oligomerization and ASC speck formation, thereby inhibiting NLRP3 inflammasome assembly and activation. Importantly, treatment with Co NSs attenuates the severity of LPS‐induced systemic inflammation and DSS‐induced colitis. This study highlights a successful strategy for utilizing cobalt‐based nanozymes to scavenge ROS and provides valuable insights into the underlying mechanism, demonstrating the potential therapeutic effects of nanozyme for the prevention and treatment of NLRP3‐associatied inflammatory diseases.