Sono-Flexocatalytic Tumor Suppression Enabled by SrTiO Nanoflexocatalysts.

Despite piezocatalytic tumor therapy offers a promising non-invasive modality for disease treatment, its application is fundamentally limited by the requirement for non-centrosymmetric piezocatalysts. To solve this critical issue, we present a novel "sono-flexocatalytic therapy" (SFT) strategy using centrosymmetric strontium titanate (SrTiO) nanocatalysts. Under ultrasound irradiation, SrTiO generates significant flexoelectric polarization due to the induced strain gradients, effectively separating charges. This drives robust redox reactions on the nanocatalyst surfaces, producing abundant cytotoxic reactive oxygen species (ROS) such as hydroxyl radicals and superoxide anions within tumor cells. The resultant ROS surge induces severe oxidative stress, mitochondrial dysfunction, and ultimately apoptosis, effectively suppressing tumor growth as validated by both in vitro and in vivo studies. Furthermore, theoretical simulations elucidate the specific strain-gradient dependent sono-flexocatalytic mechanism. This work pioneers sono-flexocatalytic tumor therapy by leveraging ultrasound-triggered flexoelectricity in SrTiO nanocatalysts, thereby not only introducing centrosymmetric biomaterials into sonocatalytic treatments but also establishing a new paradigm for pancatalytic medicine with broad material applicability.