Characteristics of Ultrasound-Driven Barium Titanate Nanoparticles and the Mechanism of Action on Solid Tumors

Sonodynamic therapy (SDT) utilizes specific sound waves to activate sonosensitizers, generating localized biological effects to eliminate tumor cells. With advancements in nanomedicine, the application of nano-acoustic sensitizers has significantly advanced the development of SDT. BaTiO₃ (BTO), an inorganic nano-acoustic sensitizer, possesses light refraction characteristics and a high dielectric constant, and can generate an electric field under ultrasound (US) stimulation. With continuous progress in multidisciplinary fields of US research, scientists have developed various types of barium titanate nanoparticles (BTNPs) to further advance SDT research and applications in tumor therapy. In this review, we present recently proposed and representative BTNPs, including their pathways of action, such as the induction of tumor cell senescence, ferroptosis, and glutathione depletion to reshape the tumor microenvironment, as well as their surface modifications. Research indicates that the mechanisms of action of ultrasound-driven BTNPs in tumor therapy are multifaceted. These mechanisms, whether utilized individually or synergistically, offer a potent and targeted strategy for cancer treatment. Furthermore, we discuss the application of BTNPs in various tumor types. Finally, we summarize the current challenges and future prospects for the clinical translation of BTNPs.