Magneto-Sono-Enhanced Nanozyme Catalysis Drives ROS-Mediated Pathogen Killing and Mitophagy-Linked Inflammation...

Bacterial pneumonia treatment faces significant challenges due to uncontrolled inflammation and rising antibiotic resistance. Excessive inflammatory cytokine release and mitochondrial dysfunction exacerbate tissue damage, contributing to the disease's progression. Mitophagy, a process that eliminates dysfunctional mitochondria, helps regulate reactive oxygen species (ROS) levels and suppress inflammation. However, efficient bacteria clearance remains critical for effective inflammatory modulation. Traditional antibiotics struggle against resistant bacteria, necessitating alternative approaches. ROS-based nanocatalytic therapies, particularly nanozymes, show potential for overcoming ROS generation limitations through external stimuli like ultrasound and magnetic fields. This study designs a sono-magneto-responsive nanozyme (BN@NF) composed of boron nanosheets (BN) and neodymium-doped iron phosphide (Nd:Fe₂P, NF), modified to form a Z-scheme heterostructure. Delivered via nebulization, BN@NF generates ROS under combined internal and external stimuli, enabling efficient bacterial killing and biofilm disruption. It also modulates inflammation by inhibiting the NF-κB pathway and promoting mitophagy, reducing pro-inflammatory cytokine release. Additionally, BN@NF enhances macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, aiding tissue repair. This approach provides a promising strategy for treating bacterial pneumonia by combining effective antibacterial action with intelligent anti-inflammatory functions.