Ultrasound-Activated Nanomaterials for Sonothermal Therapy: Mechanistic Insights and Biomedical Applications
Sonothermal therapy (STT) is an emerging noninvasive energy-based modality that leverages deeply penetrating ultrasound to activate engineered nanomaterials, converting acoustic energy into localized heat. This review systematically delineates four coupling routes between ultrasound and nanomaterials: thermoelastic, thermoviscous, and plasmonic heating; nonradiative recombination and acousto-electric coupling; thermal vibrations in carbon and conjugated systems; and cavitation heating. Design principles for STT nanomaterials are established, with guidance for pre-, intra-, and post-treatment phases, and linked to applications in tumor ablation, wound infection and healing, and implant-associated infection and regeneration. Hybrid platforms integrating STT with sonodynamic or sonocatalytic reactive oxygen species generation are discussed. Key translational barriers include the lack of quantitative and standardized metrics for conversion efficiency, the need for scalable and reproducible manufacturing aligned with Good Manufacturing Practice, limited in vivo biodistribution and biosafety data, and weak links from preclinical models to clinical endpoints. An integrated framework connecting mechanism, material design, and therapeutic outcome is proposed to guide the development of next-generation STT nanoplatforms for treatment-resistant disease.