Nitric Oxide-Actuated Titanium Dioxide Janus Nanoparticles for Enhanced Multimodal Disruption of Infectious Biofilms

Sonodynamic therapy (SDT) is promising for combating deep-seated infectious diseases by generating substantial reactive oxygen species (ROS) through the profound tissue penetration capabilities of ultrasound. However, the compact protective structures of bacterial biofilms present a formidable challenge, impeding ROS efficacy. Given that ROS have a limited diffusion range and current sonosensitizers struggle to infiltrate biofilms, complete eradication of pathogenic bacteria often remains unachieved. In this study, mesoporous titanium dioxide (TiO₂) nanoparticles are engineered asymmetrically coated with a thin layer of Ag and loaded with L-arginine (LA) to construct ultrasound-propelled nanomotors. These Ag-TiO₂-LA Janus nanoparticles demonstrate robust self-propulsion upon ultrasonic activation, allowing for deeper penetration into biofilm matrices and enhancing localized biofilm disruption through improved SDT outcomes. Additionally, the incorporation of Ag not only broadens TiO₂’s absorption spectrum but also confers photothermal capabilities upon NIR laser excitation at 808 nm. The Ag-TiO₂-LA nanomotor amalgamates TiO₂’s sonodynamic potential with Ag's photothermal properties, forging a versatile antimicrobial agent capable of efficient biofilm penetration and a synergistic antibacterial effect when subjected to dual NIR and ultrasound stimuli. This innovative, singularly-structured nanoparticle stands out as an effective combatant against bacterial biofilms and accelerates the healing process of infected wounds, showcasing potential for multifaceted clinical applications.