Theranostic potential of ultrasound-guided sonodynamic therapy for cancer: a systematic review of preclinical studies

Ultrasound-guided sonodynamic therapy (US-guided SDT) is an emerging theranostic approach that combines noninvasive tumor treatment with real-time imaging. By activating sonosensitizers through focused US to produce reactive oxygen species (ROS), SDT enables targeted tumor ablation with minimal systemic toxicity. This systematic review summarizes preclinical advancements in US-guided SDT from 2015 to 2025. Comprehensive searches across PubMed, Scopus, Web of Science, ScienceDirect, and Google Scholar identified 24 eligible studies. Extracted data included nanoplatform characteristics, parameters, imaging modalities, therapeutic outcomes, and translational potential. Across studies, US served both as an imaging and activation modality, enabling simultaneous diagnosis and therapy. Nanoparticle-based sonosensitizers enhanced ROS yield, tumor selectivity, and imaging contrast. Most studies reported significant tumor inhibition (> 70%), precise targeting, and favorable biosafety. Multifunctional nanoplatforms integrating oxygen generation, immunomodulation, or chemotherapeutic co-delivery further improved efficacy. US-guided SDT exhibits robust preclinical evidence as a dual-function imaging and treatment platform. However, lack of standardized US parameters, limited long-term safety data, and reliance on subcutaneous tumor models hinder clinical translation. Future studies should emphasize standardized dosimetry, advanced tumor models, and comprehensive biosafety evaluation to advance this promising theranostic modality toward clinical application.