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

Advanced Materials, 25 March, 2026, DOI：https://doi.org/10.1002/adma.72857

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

Jianfeng Guo, Xin Yang, Shixing Luo, Rongwei Zhang, Shuaiyi Liang, Zhengtian Li, Zhangrui Huang, Yuting Ye, Ji Luo, Zhiquan Pang, Cheng Yuan, Jinmin Zhao, Jianwei Liu, Li Zheng, Kelong Fan, Jingping Zhong

Abstract

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 (FeMn_DA/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 ([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.

文章链接：https://advanced.onlinelibrary.wiley.com/doi/10.1002/adma.72857