A Hydroxyl Radical Self-Suppling and Gsh-Depletion Hybrid Nanozyme Combined with Photothermal Therapy to Eliminate Biofilms and Eradicate Infections

Chemodynamic therapy (CDT) is considered a promising antibiofilm therapy. However, CDT is difficult to achieve the desired antibacterial effect due to low local H2O2 concentration and glutathione (GSH) overexpression in the infection microenvironment. In this article, a hybrid nanozyme (Fe3O4-CaO2-PDA) was synthesized. The Fe3O4 nanozyme possesses peroxidase activity and can catalyze the conversion of H2O2, generated by the decomposition of modified CaO2 nanoparticles under acid triggering, into hydroxyl radicals (·OH); at the same time, polydopamine (PDA) consumes GSH, destroying the local redox homeostasis and thereby enhancing CDT. More importantly, Fe3O4 nanozyme and PDA have excellent photothermal properties and can accelerate the generation of ·OH and consumption of GSH by photothermal therapy (PTT), further enhancing CDT. The antibacterial effect of CDT+PTT+GSH-depletion (Fe3O4-CaO2-PDA+L) was evaluated by bacterial Live/Dead staining, CFU colony count, and bacterial cell membrane rupture, demonstrating satisfactory antibiofilm activity. At the same time, Fe3O4-CaO2-PDA+L showed excellent antibacterial ability in vivo, and the bacterial survival rate decreased to 10% compared with the control group. Interestingly, the hybrid nanozyme also exhibits the ability to promote collagen regeneration and regulate inflammation. In summary, this study proposes a synergistic multiple enhancement strategy, successfully constructed PTT-enhanced multifunctional hybrid nanozyme for efficient CDT anti-infection therapy.