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 CuO nanoparticles (NPs) is successfully constructed via a simple, fast and low-cost approach. The CuO NPs exhibit high sensitivity to overexpressed HS and HO in the bacterial infection microenvironment. After in situ injection, the CuO NPs will rapidly react with the endogenous HS to generate CuS NPs, which exhibits high absorbance in the second near-infrared (NIR-II) biowindow. The CuS 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), HS-activated photothermal antibacterial therapy (PTAT) can realize excellent antibacterial performance under 1060 nm laser irradiation. Meanwhile, the CuO NPs can effectively catalyze HO 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 CuO 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.