Enhanced chemodynamic therapy for biofilm eradication: A self-supplied H2O2 nanoplatform with integrated photothermal property

Abstract

Bacterial biofilm infections, characterized by high mortality and challenging recovery, pose a significant global health risk. Developing innovative antibacterial materials and therapies, particularly those that mitigate resistance, is essential for effectively addressing biofilm-associated infections. Chemical dynamic therapy (CDT), which relies on hydroxyl radicals (·OH) generated from hydrogen peroxide (H₂O₂) to eliminate bacteria, has demonstrated potential in treating planktonic infections. However, traditional CDT is less effective against biofilm-related infections due to limited endogenous H₂O₂ and the protective extracellular polymeric matrix within biofilms. In this study, a composite nanoplatform based on CuO₂ with self-supplying H₂O₂ capabilities and Fe₃O₄ with photothermal properties was designed to improve CDT efficacy for biofilm eradication. The Fe₃O₄/CuO₂ composite nanoparticles (FC NPs) were synthesized by incorporating CuO₂ into hollow mesoporous Fe₃O₄ using an in-situ growth technique. Within the mildly acidic biofilm microenvironment, CuO₂ decomposes to release Cu²⁺ and H₂O₂. The Cu²⁺ subsequently catalyzes the Fenton-like conversion of the released H₂O₂ into ·OH. Concurrently, near-infrared (NIR) irradiation of Fe₃O₄ generates significant heat, boosting ·OH production and increasing bacterial membrane permeability, thereby enhancing bacterial vulnerability to ·OH. This nanoplatform demonstrated remarkable CDT efficacy, eradicating over 99.99% of methicillin-resistant Staphylococcus aureus (MRSA) and 99.97% of Pseudomonas aeruginosa biofilms within five minutes of NIR irradiation in vitro. Furthermore, in vivo experiments validated the nanoplatform's ability to eradicate biofilms and facilitate the healing of MRSA-infected wounds without adverse effects. This H₂O₂ self-supplying and heat-enhancing approach presents a promising strategy to overcome the limitations of CDT in biofilm-related infection treatment.