Nanosonosensitizers in antibacterial sonodynamic therapy: mechanism exploration, activity enhancement strategies, and current status of antibacterial applications

Sonodynamic therapy (SDT), as a highly promising alternative antibacterial modality, achieves non-invasive treatment of infected sites by activating sonosensitizers with ultrasound (US) to generate reactive oxygen species (ROS). However, its therapeutic efficacy largely depends on the performance of the sonosensitizers. The advent of nanoscience and technology has brought significant breakthroughs in this field, through the design of high-performance nanomaterials to address the challenges of chemical stability, bioavailability, and rapid clearance that conventional organic sonosensitizers face. This review details the therapeutic mechanisms of inorganic nanosonosensitizer-mediated antibacterial sonodynamic therapy (aSDT). It then, based on limitations of conventional inorganic sonosensitizers (e.g., rapid charge carrier recombination and a hypoxic infection microenvironment), summarizes cutting-edge strategies for optimizing nanosonosensitizer performance. These strategies are mainly divided into four directions: (1) optimization of the surface structure of materials: morphological engineering; (2) optimization of the internal structure of materials: defect engineering; (3) enhancement of overall performance through the construction of composite materials: phase engineering and interface engineering; (4) emerging synergistic enhancement strategies: hydrogel delivery systems, nanozyme catalytic systems, and metal-organic framework (MOF) carrier systems. Furthermore, this review discusses the applications and therapeutic efficacy of advanced nanosonosensitizers in antibacterial therapy. Finally, this review provides an outlook on the future directions and challenges in this field, aiming to translate aSDT into a safe, targeted, and effective modality for application in complex environments.