DISCUSSIONIn summary, we have developed an integrated nanozyme withthe ability to catalyze cascade reactions for ROS elimination. Theintegrated nanozyme not only has two spatially separated activesites, which can mimic SOD and CAT, but also has a confinementeffect that enhances the overall reaction rate by increasing mass-transferefficiency and reducing the transfer time between catalyticcenters, as demonstrated by kinetic analysis. In vitro experimentsshowed that the cascade nanozyme has outstanding ROS-scavengingactivity, excellent biocompatibility, and good aqueous dispersibility.We established an inflammatory animal model to evaluate the anti-ROSability of the cascade nanozyme in vivo. To our delight, the cascade nanozyme exhibited superior therapeutic efficacy towardboth an UC and CD model state in mice, as compared to mice treatedwith an unintegrated mixture of the two nanozymes. Furthermore,in these animal models, we successfully achieved effective relief ofboth IBDs by optimizing the concentration of the cascade nanozyme.This work not only demonstrates that MOF-based nanozymeshave excellent ROS-scavenging activities for in vivo inflammatorytreatment but also provides a promising strategy to constructintegrated nanozymes with multifunctional active sites for futureapplications.MATERIALS AND METHODS