NIR-Activated Ag₂S Quantum Dots for Synergistic Immunomodulation and Precision Therapy of Refractory Osteomyelitis

Staphylococcus aureus (S. aureus) is a predominant clinical pathogen responsible for a wide range of infections. By forming biofilms during infection, S. aureus evades conventional therapies, leading to persistent infections and treatment failure. To address this challenge, we employed silver sulfide quantum dots (Ag₂S QDs) for near-infrared (NIR) phototherapy. In vitro, the nanoagent achieved >99.99% killing of S. aureus within 10 minutes and reduced biofilm biomass by >58%. In a murine osteomyelitis model, a single NIR treatment reduced bacterial loads by 71.83% on implants and 59.18% in bone tissue, while also suppressing key inflammatory cytokines, with local macrophage polarization shifting from an M1-dominant to an M2-dominant phenotype. Histopathological and micro-CT analyses indicated attenuated bone destruction. The nanoagent showed favorable biosafety, with no systemic toxicity in major organs and osteoblast viability >75% at therapeutic concentrations. Together, these results demonstrate a phototherapeutic strategy with combined antibacterial and anti-biofilm effects, supporting its potential as an adjuvant approach for managing refractory osteomyelitis.