Reengineering Aligned D‐Orbital Energy Levels in FeMn Dual‐Atom Nanozyme Inhibits Pyroptosis for Effective Alleviation of Inflammatory Diseases

Abstract

ABSTRACT Pyroptosis inhibition via Fe single‐atom nanozymes is promising for inflammation therapy, but the common Fe‐N 4 configuration restricts oxygen intermediate desorption and lacks cooperative sites, thus limiting catalytic performance. To overcome this, we develop a FeMn dual‐atom nanozyme supported on oxygen‐nitrogen‐doped bamboo‐like carbon nanotubes (FeMn DA /BCNT). Through the precise alignment of Fe and Mn 3 dz 2 orbital energy levels by the electron‐delocalized BCNT support in the FeMn‐N/O active center, thereby lowering the dissociation energy barrier for * O 2 or * H 2 O molecules, promoting O─O bond cleavage to bypass toxic ─OOH species, and thus accelerating the enzyme‐like kinetics. Combined with a hierarchical porous bamboo‐like structure of the BCNT that enhances high specific surface, atom exposure, and mass transfer, the FeMn DA /BCNT nanozymes exhibit potent superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)‐like activities. Further encapsulation with a macrophage membrane ([MM]FeMn DA /BCNT) confers excellent biocompatibility and active targeting ability toward inflammatory sites. The resulting [MM]FeMn DA /BCNT nanozymes target the inflammatory microenvironment, scavenges ROS, restores mitochondrial function, and suppresses NLRP3 inflammasome activation, thereby inhibiting pyroptosis. In vivo, [MM]FeMn DA /BCNT nanozymes show good biocompatibility and efficacy in treating osteoarthritis, acute liver injury, and acute kidney injury. This work provides a novel strategy for inflammatory disease therapy using a biomimetic dual‐atom nanozyme.