Bio-heterointerface charging through ultrasound-boosted extracellular and intracellular electron transfer for rapid bacterial killing

The deep-seated drug-resistant bacterial infection is one of the most noticeable public-health threat owing to poor drug therapeutic effect, high recurrence, and devastating complication. Herein, we propose a bactericidal strategy of bio-heterointerface charging through ultrasound-boosted bacterial extracellular and intracellular electron transfer for eradicating implant-related drug-resistant bacterial infection, where a TiO₂-modified porphyrin-based two-dimensional metal-organic framework (2DMOF-TiO₂) is selected as a sonosensitizer. The ultrasound-boosted extracellular and intracellular electron transfer between methicillin-resistant Staphylococcus aureus and 2DMOF-TiO₂ induces rapid reactive oxygen species (ROS) burst surrounding bacterial outer and inner, contributing to intracellular oxidation, membrane potential decrease (∼5 mV), membrane disruption, and pyrimidine metabolism disorder, thus causing bacterial death. The in vivo results of 2DMOF-TiO₂ implant exhibit rapid sonocatalytic anti-infection and enhanced osseointegration at bone-implant interface. This platform may inspire the universal thinking about ultrasound-boosted extracellular and intracellular electron-transfer-induced ROS and provide a superior therapeutic candidate for various deep-seated infectious diseases.