A self-supplied hydrogen peroxide and nitric oxide-generating nanoplatform enhances the efficacy of chemodynamic therapy for biofilm eradication

Bacterial biofilms present a profound challenge to global public health, often resulting in persistent and recurrent infections that resist treatment. Chemodynamic therapy (CDT), leveraging the conversion of hydrogen peroxide (H2O2) to highly reactive hydroxyl radicals (center dot OH), has shown potential as an antibacterial approach. Nonetheless, CDT struggles to eliminate biofilms due to limited endogenous H2O2 and the protective extracellular polymeric substances (EPS) within biofilms. This study introduces a multifunctional nanoplatform designed to self-supply H2O2 and generate nitric oxide (NO) to overcome these hurdles. The nanoplatform comprises calcium peroxide (CaO2) for sustained H2O2 production, a copper-based metal-organic framework (HKUST-1) encapsulating CaO2, and l-arginine (l-Arg) as a natural NO donor. When exposed to the acidic microenvironment within biofilms, the HKUST-1 layer decomposes, releasing Cu2+ ions and l-Arg, and exposing the CaO2 core to initiate a cascade of reactions producing reactive species such as H2O2, center dot OH, and superoxide anions (center dot O-2(-)). Subsequently, H2O2 catalyzes l-Arg to produce NO, which disperses the biofilm and reacts with center dot O-2(-) to form peroxynitrite, synergistically eradicating bacteria with center dot OH. In vitro assays demonstrated the nanoplatform's remarkable antibiofilm efficacy against both Gram-positive Methicillin-resistant Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa, significantly reducing bacterial viability and EPS content. In vivo mouse model experiments validated the nanoplatform's effectiveness in eliminating biofilms and promoting infected wound healing without adverse effects. This study represents a breakthrough in overcoming traditional CDT limitations by integrating self-supplied H2O2 with NO's biofilm-disrupting capabilities, offering a promising therapeutic strategy for biofilm-associated infection.