Advances in sonodynamic therapy of multifunctional nanomaterials for bacterial infectious diseases

Bacterial infectious diseases are in urgent need of novel therapeutic strategies due to increased drug resistance and complex host-pathogen interaction mechanisms. This review systematically summarizes recent advances in sonodynamic therapy (SDT) utilizing multifunctional nanomaterials for the treatment of bacterial infections. The design and functionality of these nanomaterials predominantly rely on principles of coordination chemistry. Beginning with an analysis of pathogenesis, this article examines the dynamic interplay between bacterial virulence factors and host immune responses, as well as the evolution of drug resistance and patterns of bacterial colonization and dissemination. Furthermore, it elaborates on the mechanisms by which SDT induces synergistic structural damage to bacteria through cavitation-generated sonomechanical, sonochemical, and sonothermal effects. For six types of clinically refractory infections, such as myositis and osteomyelitis, nanomaterials can significantly improve the therapeutic effect through targeted delivery, enhanced stability of sonosensitizers and local acoustic field response. Combining photodynamic, photothermal, herbal active ingredients and immunotherapy further revealed the potential of SDT to synergize multiple therapies in bactericidal and host microenvironment modulation. Although SDT has demonstrated considerable advancements in antimicrobial treatment, several significant challenges remain. These include concerns regarding the biocompatibility and long-term safety of nanomaterials, the absence of standardized clinical protocols, the insufficient development of integrated theranostic platforms, and uncertainties surrounding the clinical safety and efficacy of current treatment strategies. Future research efforts should prioritize the design and synthesis of novel sonosensitizers, the refinement of ultrasound parameters, and the advancement of multimodal imaging-guided combination therapies based on SDT. Furthermore, rigorous evaluation of treatment safety and efficacy through well-designed large-animal infection models is essential to accelerate the clinical translation of SDT. Such developments are critical for addressing the growing need for precise therapeutic strategies against bacterial infections in the post-antibiotic era.