Ultrasound-Activated “Ros-Microjet” For Precision Oral Pathogens Eradication

Traditional ROS-mediated antibacterial strategies for oral infectious diseases face a critical limitation: unrestricted diffusion of free ROS causes indiscriminate oxidative damage to both pathogens and host cells. This study aims to overcome this challenge through the development of an ultrasound-responsive bio-heterojunction system. Designed and synthesized an ultrasound-responsive bio-heterojunction composed of BaTiO₃, CeO₂, and glucose oxidase (GOx), designated as BaTiO₃@CeO₂-GOx (BCG). Evaluated the system's responsiveness to ultrasound stimulation and its ability to generate and direct ROS. Conducted in vitro and in vivo experiments to assess antimicrobial efficacy and safety. Investigated the mechanism of bacterial killing through analysis of bacterial liquid-liquid phase separation homeostasis. Compared mitochondrial autophagy levels between the "ROS-MicroJet" strategy and conventional ROS therapies. BaTiO₃ harnessed piezocatalytic activity to generate ROS under ultrasonication while simultaneously producing microbubbles through sonocavitation. ROS-laden microbubbles collapsed at bacterial cell envelopes, creating high-velocity "ROS-MicroJets" that precisely delivered oxidative attack to bacterial biomolecules. CeO₂ effectively scavenged excess free ROS, protecting host cells from oxidative damage. The BCG system demonstrated exceptional antibacterial efficacy in both in vitro and in vivo models. The "ROS-MicroJet" strategy disrupted bacterial liquid-liquid phase separation homeostasis. Compared to conventional ROS therapies, the BCG system significantly reduced mitochondrial autophagy in cells. The ultrasound-activated "ROS-MicroJet" strategy successfully addresses the longstanding challenge of indiscriminate oxidative damage in ROS-mediated antibacterial therapies. This approach provides a promising therapeutic strategy for oral infectious diseases.