A Photo-Therapeutic Nanocomposite with Bio-Responsive Oxygen Self-Supplying Combats Biofilm Infections and Inflammation from Drug-Resistant Bacteria

The use of non-antibiotic strategies to combat refractory drug-resistant bacterial infections, especially biofilms and accompanying inflammation, has recently aroused widespread interest. Herein, a photo-therapeutic nanocomposite with bio-responsive oxygen (O₂) self-supplying is introduced by integrating manganese dioxide (MnO₂) nanozymes onto photosensitizer (indocyanine green, ICG)-loaded mesoporous polydopamine nanoparticles (MPDA), namely MI-MPDA NPs. MI-MPDA can activate O₂ generation in the infection microenvironment, thereby effectively alleviating biofilm hypoxia. Under near-infrared light (NIR) irradiation, continuous O₂ supplying further boosts the level of singlet oxygen (¹O₂), enabling robust biofilm elimination through O₂-potentiated photodynamic/photothermal therapy. Interestingly, MI-MPDA down-regulates the factor expression of inflammatory signaling pathways through MnO₂-mediated reactive oxygen species scavenging, which ameliorates the inflammatory condition. Meanwhile, O₂ supplying prevents the M1-phenotype switch of macrophages from the overexpression of hypoxia-inducible factor-1α (HIF-1α), thereby prompting macrophage reprogramming toward pro-regenerative M2-phenotype. In the mouse models of subcutaneous implant-associated infection caused by methicillin-resistant Staphylococcus aureus (MRSA) biofilms and burn infection caused by Pseudomonas aeruginosa biofilms, NIR-irradiated MI-MPDA not only effectively eliminates the formed biofilms, but also alleviates the oxidative stress and accompanying inflammation, and drives the cascade reaction of immunomodulation-wound healing. Overall, this O₂-potentiated photo-therapeutic strategy provides a reliable tool for combating biofilm infections and inflammation from drug-resistant bacteria.