Pyroptosis inhibition via Fe single-atom nanozymes is promising for inflammation therapy, but the common Fe-N4 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 (FeMnDA/BCNT). Through the precise alignment of Fe and Mn 3dz2 orbital energy levels by the electron-delocalized BCNT support in the FeMn-N/O active center, thereby lowering the dissociation energy barrier for *O2 or *H2O 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 FeMnDA/BCNT nanozymes exhibit potent superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)-like activities. Further encapsulation with a macrophage membrane (MMFeMnDA/BCNT) confers excellent biocompatibility and active targeting ability toward inflammatory sites. The resulting MMFeMnDA/BCNT nanozymes target the inflammatory microenvironment, scavenges ROS, restores mitochondrial function, and suppresses NLRP3 inflammasome activation, thereby inhibiting pyroptosis. In vivo, MMFeMnDA/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.
Guo et al. (Wed,) studied this question.