A potassium-based single-atom catalyst enables acute lung injury immunotherapy in mice by inhibiting macrophage
Xiangyu Lu1,2,3, Xuan Shi1, Yanmin Jian4
1Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Abstract:
Acute lung injury (ALI), which can have a mortality rate approaching 40%, lacks effective therapies. Macrophage pyroptosis represents a pro-inflammatory event and a potential therapeutic target. Here, we report a single-atom immunomodulator, a potassium-based single-atom catalyst (K-SAC) with K-N4 sites, that suppresses macrophage pyroptosis for ALI therapy through antioxidant catalysis. Constructed from biocompatible potassium, the most abundant intracellular metal in humans, K-SAC displays potent superoxide dismutase- and catalase-like activities, with the underlying mechanisms revealed by density functional theory simulations. Following preferential macrophage uptake, K-SAC scavenges reactive oxygen species, downregulates gasdermin D and its N-terminal fragment, activates endosomal sorting complexes required for transport-mediated membrane repair, and promotes membrane phospholipid remodeling, thereby effectively inhibiting macrophage pyroptosis. Notably, this catalytic membrane repair mechanism offers a versatile strategy for restoring membrane integrity. Such catalytic inhibition of pyroptosis preserves pulmonary immune homeostasis and ameliorates lipopolysaccharide- or cecal ligation and puncture-induced ALI, establishing a catalytic immunotherapeutic approach using a physiologically abundant element for therapeutic applications.
