Ultrasound-activated MoS₂@Fe₃O₄ nanoplatform orchestrates biofilm disruption and immune reprogramming in implant-associated infections

Implant-associated infections (IAIs), particularly those caused by antibiotic-resistant pathogens and protected by biofilms, remain a formidable challenge in orthopedic surgery due to limited antibiotic efficacy and sustained local immunosuppression. Addressing this dual bottleneck, we report a multifunctional MoS₂@Fe₃O₄ heterostructure nanocomposite that enables ultrasound (US)-triggered piezocatalytic antibacterial therapy coupled with immune microenvironment remodeling. The nanoplatform integrates the piezoelectric polarization of MoS₂ and the Fenton-like catalytic activity of Fe₃O₄ to achieve efficient charge separation, interfacial polarization, and enhanced Fe³⁺/Fe²⁺ cycling, generating high levels of ROS (•OH, •O₂⁻, ¹O₂) under low-intensity US irradiation. These reactive species effectively disrupt MRSA biofilms, promote bacterial membrane rupture, and expose pathogen-associated antigens. Importantly, this treatment activates the cGAS-STING signaling axis in dendritic cells, enhances M1-type macrophage polarization, and triggers coordinated innate and adaptive immune responses. In a murine subcutaneous IAI model, MoS₂@Fe₃O₄ + US not only eradicated biofilm infections and reduced myeloid-derived suppressor cell (MDSC) infiltration, but also induced robust CD4⁺/CD8⁺ T cell activation and memory B/T cell formation, effectively preventing infection recurrence after implant replacement. This work presents a paradigm-shifting, non-antibiotic immunotherapeutic strategy that integrates catalytic disinfection, immune activation, and long-term protection in a single nanoplatform. By overcoming key limitations of current treatments, our approach offers substantial promise for improving clinical outcomes in IAIs and advancing the field of immune-interactive nanomedicine.