A pH‐Switchable Cerium Single‐Atom Enzyme for Peri‐Implantitis Therapy via JAK‐STAT Signaling Axis‐Mediated Macrophage Reprogramming
Xiaomin Xia, Haojie Wu, Xingyun Li, Lining Liu, Kaiqing Song, Jinpei Cui, Jie Liu, Jiaxuan Yin, Emtiaz Ahmed, Yusuke Yamauchi, Xue LiABSTRACT
The development of high‐performance, environmentally adaptive enzyme‐mimicking catalysts for the treatment of peri‐implantitis (PI) is of great importance yet remains highly challenging. Herein, we report a high‐performance cerium single atom on B, N co‐doped carbon nanotubes enzyme (SAzyme), denoted as Ce‐BNC. Benefitting from its unique N/O‐coordinated electronic environment and reversible Ce 3+ /Ce 4+ redox cycle, Ce‐BNC exhibits an intrinsic pH‐switchable catalytic function, with acidic conditions favoring peroxidase (POD)‐likeactivity for hydrogen peroxide (H 2 O 2 ) activation and reactive oxygen species (ROS)‐mediated antibacterial effects, whereas relatively neutral conditions promote superoxide dismutase (SOD)‐ and catalase (CAT)‐like enzymatic cascades for ROS conversion and oxygen generation. Through this pH‐switchable catalytic transition, Ce‐BNC enables dynamic switching between oxidative antimicrobial activity and antioxidative microenvironment modulation. Mechanistically, this pH‐switchable enzymatic relay is thermodynamically governed by reduced Gibbs free‐energy barriers. This antioxidant effect further disrupts the M1 macrophage/IL‐6‐JAK/STAT signaling axis, thereby remodeling the inflammatory microenvironment. This work presents a microenvironment‐adaptive catalytic platform with programmable bimodal activities, offering a promising paradigm for the intelligent and staged treatment of inflammatory diseases.