Infection microenvironment-activated nanoparticles for NIR-II photoacoustic imaging-guided photothermal/chemodynamic synergistic anti-infective therapy

Subcutaneous abscesses caused by drug-resistant bacteria pose huge challenges to human health. The design of infection microenvironment-activated biomaterials has an advantage for the diagnosis and treatment of infective diseases due to its high specificity and efficiency. Herein, a novel theranostic platform based on Cu₂O nanoparticles (NPs) is successfully constructed via a simple, fast and low-cost approach. The Cu₂O NPs exhibit high sensitivity to overexpressed H₂S and H₂O₂ in the bacterial infection microenvironment. After in situ injection, the Cu₂O NPs will rapidly react with the endogenous H₂S to generate Cu₉S₈ NPs, which exhibits high absorbance in the second near-infrared (NIR-II) biowindow. The Cu₉S₈ NPs serving as NIR-II photoacoustic contrast agents can exactly distinguish between inflammatory and normal tissues. With the guidance of NIR-II photoacoustic imaging (PAI), H₂S-activated photothermal antibacterial therapy (PTAT) can realize excellent antibacterial performance under 1060 nm laser irradiation. Meanwhile, the Cu₂O NPs can effectively catalyze H₂O₂ at the site of inflammation to produce hydroxyl radicals with strong antibacterial property via Fenton-like reaction, resulting in the damage of bacterial cell membrane. Furthermore, the application of Cu₂O NPs can enhance epidermic migration and facilitate the re-epithelialization of the infected skin. In vivo experiment shows that 97.9% methicillin-resistant Staphylococcus aureus are eliminated by the synergistic PTAT and chemodynamic antibacterial therapy.