Ultrasound-activated sonothermal-catalytic synergistic therapy via asymmetric electron distribution for bacterial wound infections

Abstract

Antibiotic-resistant bacterial infections present a growing global health challenge, requiring innovative therapeutic solutions to overcome current limitations. We introduce boron-integrated bismuth oxide (B–BiO₂) nanosheets with an asymmetrically distributed electronic structure for ultrasound-activated synergistic sonothermal and catalytic therapy. Boron incorporation enhances local electron density distribution, optimizing charge separation and significantly improving sonothermal and catalytic efficiency, as validated by density functional theory calculations. These nanosheets exhibit dual functionality, effectively generating localized heat and reactive oxygen species (ROS) under ultrasound, leading to 99.999 % antibacterial efficacy against multidrug-resistant pathogens by disrupting bacterial membranes, as demonstrated through all-atom simulations and in vitro experiments. The simulations further reveal that sonothermal conversion effects enhance bacterial membrane fluidity and induce structural defects, amplifying ROS-induced oxidative damage and membrane destabilization. In vivo, B–BiO₂ nanosheets accelerate wound healing in methicillin-resistant Staphylococcus aureus (MRSA)-infected murine models, achieving 99.8 % closure by day 14 by reducing inflammation and promoting angiogenesis and tissue regeneration. Transcriptomic analysis highlights the activation of extracellular matrix remodeling, angiogenesis, and autophagy pathways, underscoring the nanosheets’ therapeutic potential. This study establishes ultrasound-activated B–BiO₂ nanosheets as a novel nanotherapeutic platform, leveraging asymmetric electron distribution to synergistically combat drug-resistant infections and promote effective wound healing.