Bimetallic biomimetic catalytic STING sensitizer for coordinating innate and adaptive immune responses against biofilm infections.

Implant-related infections remain refractory because bacterial biofilms create a physical barrier and are accompanied by local immune dysfunction. Here, we develop a biomimetic metallo-immunocatalytic nanoplatform by cloaking a pH-responsive manganese-iron layered double hydroxide (MFH) core with an M1 macrophage membrane to form MFHM. This design integrates a structurally coupled Mn-Fe catalytic lattice with a functionally preserved biointerface, enabling infection-targeted delivery, colloidal stability, and microenvironment-responsive ion release. Within the acidic biofilm niche, the electronically coupled MFH core promotes Fe/Mn redox cycling and sustains Fenton-like reactive oxygen species generation, thereby disrupting extracellular polymeric substances, damaging bacterial membranes, and perturbing bacterial metal homeostasis. Concurrently, released Mn2+ and redox-active Fe species act as immunomodulatory cues that enhance cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) and nuclear factor κB (NF-κB) signaling, promote pro-inflammatory macrophage polarization and phagocytic function, and facilitate dendritic-cell maturation and downstream adaptive immune engagement. In a methicillin-resistant Staphylococcus aureus implant-associated infection model, MFHM markedly reduces bacterial burden, promotes tissue repair, and elicits a coordinated immune response that may support protective adaptive immunity, without apparent treatment-related systemic toxicity. These findings establish a catalytic-immune framework based on a biomimetic bimetallic nanostructure and highlight its potential therapeutic application in recalcitrant biofilm-associated infections.