Calcium manganese-based pancatalytic nanozyme as cell pyroptosis inhibitor for efficient inflammatory bowel disease treatment

Abstract

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder marked by dysregulated immune responses and pyroptosis of intestinal epithelial cells, a type of programmed cell death that aggravates inflammation. Current therapeutic strategies frequently encounter limitations in both efficacy and specificity. Herein, we developed a calcium manganese-based (CaMn2O4) pancatalytic nanozyme designed to mitigate pyroptosis and alleviate IBD symptoms. The calcium manganese-based nanozyme exhibits dual enzyme (catalase and superoxide dismutase)-mimetic catalytic activities, scavenging reactive oxygen species and suppressing GSDMD cleavage, a key mediator of pyroptosis. In vitro studies demonstrated that CaMn2O4 nanozyme significantly reduced pyroptotic cell death in lipopolysaccharide/nigericin-stimulated cells. In a murine colitis model, CaMn2O4-based nanozyme treatment attenuated inflammatory infiltration, preserved epithelial barrier integrity, and downregulated pyroptosis-related markers. This study highlights the potential of pancatalytic nanotherapy targeting pyroptosis as a novel strategy for IBD treatment.