Thermo-responsive tri-modal antimicrobial platform for precise biofilm removal and enhanced wound healing

Abstract A bacterial-specific therapeutic nanosystem (HMAPH) is developed based on biodegradable hollow mesoporous Prussian blue encapsulating photosensitizer methylene blue (MB), followed by modification with gold nanoparticles, polymyxin B (PMB), and hyaluronic acid (HA) to improve near-infrared (NIR) response release characteristics, specificity, and hydrophilicity. In this system, hyaluronic acid is decomposed under the action of hyaluronidase, and the exposed nanomaterials specifically bind the outer membrane of Pseudomonas aeruginosa ( P. aeruginosa ) through PMB to increase the membrane sensitivity to photodynamic treatment. Under dual light irradiation, a large amount of iron ions released by HMAPH can undergo Fenton reaction with H 2 O 2 in bacteria to generate hydroxyl radicals (▪OH), enabling photothermal properties to directly kill cells by hyperthermia. Additionally, the photodynamic activity of MB released by photoinduced activation can generate reactive oxygen species, achieving synergistic and effective inhibition of P. aeruginosa . HMAPH can also inhibit and disrupt biofilm formation and down-regulate the expression of virulence factors. In vivo experiments revealed that HMAPH can accelerate P. aeruginosa -infected wound healing by promoting angiogenesis and skin regeneration, inhibiting inflammatory response, and promoting M1 to M2 polarization. Our work proposes a strategy against bacteria and biofilms through a synergistic photothermal-photodynamic-Fenton reaction, opening up new prospects for combating biofilm-associated infections.