Thermo-responsive cascade antimicrobial platform for precise biofilm removal and enhanced wound healing.

BACKGROUND

Bacterial infection, tissue hypoxia and inflammatory response can hinder infected wound repair. This study aimed to develop a multifunctional specific therapeutic photo-activated release nanosystem [HMPB@MB@AuNPs@PMB@HA (HMAPH)] by loading photosensitizer methylene blue (MB) into hollow mesoporous Prussian blue nanostructures and modifying the surface with gold particles, polymyxin B (PMB) and hydrophilic hyaluronic acid.

METHODS

The HMAPH was characterized using transmission electron microscopy, UV-vis, Fourier-transform infrared spectroscopy, X-ray diffraction and X-ray photon spectroscopy. The photothermal performance, iron ion release and free radical generation of the HMAPH were measured under different conditions to investigate its thermo-responsive cascade reaction. The antibacterial ability of HMAPH was investigated using live/dead fluorescence tests. The morphology and membrane integrity of () were investigated using transmission electron microscopy. The anti-biofilm activity of HMAPH was evaluated using crystal violet and SYBR Green I staining. Finally, we established a mouse model of a skin wound infected by to confirm the effectiveness of HMAPH. We used immunofluorescent staining, hematoxylin-eosin staining, Masson staining and enzyme-linked immunosorbent assay to examine whether HMAPH promoted wound healing and reduced inflammatory damage.

RESULTS

In this study, hyaluronic acid was decomposed under the action of hyaluronidase. Also, the exposed nanomaterials specifically bound to the outer membrane of through PMB to increase the membrane sensitivity to photodynamic treatment. Under dual-light irradiation, a large amount of iron ions released by HMAPH underwent a Fenton reaction with HO in bacteria to generate hydroxyl radicals (•OH), enabling direct killing of cells by hyperthermia. Additionally, the photodynamic activity of MB released by photo-induced activation led to the generation of reactive oxygen species, achieving synergistic and effective inhibition of . HMAPH also inhibited biofilm formation and downregulated the expression of virulence factors. experiments revealed that HMAPH accelerated the healing of -infected wounds by promoting angiogenesis and skin regeneration, inhibiting the inflammatory response and promoting M1 to M2 polarization.

CONCLUSIONS

Our study proposed a strategy against bacteria and biofilms through a synergistic photothermal-photodynamic-Fenton reaction, opening up new prospects for combating biofilm-associated infections.