TiO2Nanoparticles as A Sonosensitizer for Sonodynamic Therapy: A Systematic Review of in Vitro Studies

Abstract

Background: In recent years, titanium dioxide (TiO2) nanoparticles have demonstrated suitable potential for use in sonodynamic therapy due to their stability and non-toxicity. Despite this, systematic in vitro studies are rare. An aim of this systematic review is to investigate the increasing role of TiO2nanoparticles in sonodynamic therapy as well as factors contributing to their efficacy. Methods: A comprehensive literature search was conducted on Scopus, Web of science, and PubMed. A total of 14 studies that met the inclusion criteria were selected and cell viability was examined under sonodynamic therapy with and without TiO2nanoparticles in different cell lines. Findings: The findings indicated that TiO₂ nanoparticles have minimal intrinsic toxicity but significantly enhance cancer cell death when combined with ultrasound waves. Factors such as ultrasound intensity, the size, and the band gap of TiO2 nanoparticles play a critical role in this synergistic effect. Conclusion: A reduced band gap in TiO₂ nanoparticles leads to increased generation of reactive oxygen species (ROS), thereby enhancing cell death. Moreover, surface coatings such as polyethylene glycol (PEG) and cancer cell membranes improve the stability, dispersion, and targeting capability of the nanoparticles. Optimal ultrasound intensity further maximizes therapeutic efficiency. In vitro studies suggest that TiO₂ nanoparticles are effective sonosensitizers for SDT against cancer cells. Optimizing nanoparticle characteristics and ultrasound parameters can enhance treatment efficacy while minimizing side effects on healthy tissues. © 2026, Isfahan University of Medical Sciences(IUMS). All rights reserved.