Piezoelectric Ba_0.85Sr_0.15TiO₃ Nanosonosensitizer with Nitric Oxide Delivery for Boosting Cancer Therapy

Abstract The efficacy of sonodynamic therapy (SDT) mainly relies on the sonosensitizers, which generate reactive oxygen species (ROS) upon ultrasound (US) stimulation. However, the limited availability of high‐efficiency sonosensitizers hampers the therapeutic effectiveness of SDT as a standalone modality. In this work, a robust sonodynamic and gas cancer therapeutic platform is constructed based on strontium (Sr) doped barium titanate (BST) piezoelectric nanoparticles functionalized with L‐arginine (BST@LA). The doping of Sr into A site of the ABO₃ piezoelectric nanocrystals not only introduces oxygen vacancies into the nanoparticles and enhance the intrinsic piezoelectricity, but also narrows the semiconductor band gap and enhances charge carrier migration, all of which facilitate the sonodynamic production of superoxide anion (•O₂⁻) and hydroxyl radical (•OH). In addition, the generated ROS promotes the decomposition of the surface‐tethered LA, enabling the controlled release of nitric oxide (NO) gas at the tumor site, thereby achieving a combination therapeutic effect. In vivo experiments exhibit remarkable tumor suppression rate (89.5%) in 4T1 tumor mice model, demonstrating the effectiveness of this strategy. The ion doping and oxygen vacancy engineering to improve sonosensitizers, along with the synergistic combination of sonodynamic and gas therapy, provides promising avenues for improving cancer therapy.