Piezocatalytic Tumor Therapy by Ultrasound-Triggered and BaTiO3-Mediated Piezoelectricity

Ultrasound theranostics features non-invasiveness, minor energy attenuation, and high tissue-penetrating capability, and is playing ever-important roles in the diagnosis and therapy of diseases in clinics. Herein, ultrasound is employed as a microscopic pressure resource to generate reactive oxygen species (ROS) for piezocatalytic tumor therapy under catalytic mediation by piezoelectric tetragonal BaTiO₃ (T-BTO). Under the ultrasonic vibration, the electrons and holes are unpaired and they are separated by the piezoelectricity, resulting in the establishment of a strong built-in electric field, which subsequently catalyzes the generation of ROS such as toxic hydroxyl (^•OH) and superoxide radicals (^•O₂⁻) in situ for tumor eradication. This modality shows intriguing advantages over typical sonoluminescence-activated sonodynamic therapy, such as more stable sensitizers and dynamical control of redox reaction outcomes. Furthermore, according to the finite element modeling simulation, the built-in electric field is capable of modulating the band alignment to make the toxic ROS generation energetically favorable. Both detailed in vitro cellular level evaluation and in vivo tumor xenograft assessment have demonstrated that an injectable T-BTO-nanoparticles-embedded thermosensitive hydrogel will substantially induce ultrasound irradiation-triggered cytotoxicity and piezocatalytic tumor eradication, accompanied by high therapeutic biosafety in vivo.