Two‐Dimensional Atomically Thin Piezoelectric Nanosheets for Efficient Pyroptosis‐Dominated Sonopiezoelectric Cancer Therapy

Sonopiezocatalytic therapy is an emerging therapeutic strategy that utilizes ultrasound irradiation to activate piezoelectric materials, inducing polarization and energy band bending to facilitate the generation of reactive oxygen species (ROS). However, the efficient generation of ROS is hindered by the long distance of charge migration from the bulk to the material surface. Herein, atomically thin Bi2O2(OH)(NO3) (AT‐BON) nanosheets are rationally engineered through disrupting the weaker hydrogen bonds within the [OH] and [NO3] layer in the bulk material. The ultrathin structure of AT‐BON piezocatalytic nanosheets shortens the migration distance of carriers, expands the specific surface area, and accelerates the charge transfer efficiency, showcasing a natural advantage in ROS generation. Importantly, the non‐centrosymmetric polar crystal structure grants the nanosheets the ability to separate electron‐hole pairs. Under ultrasonic mechanical stress, Bi2O2(OH)(NO3) nanosheets with the remarkable piezoelectric feature exhibit the desirable in vivo antineoplastic outcomes in both breast cancer model and liver cancer model. Especially, the AT‐BON‐induced ROS bursts lead to the activation of the Caspase‐1‐driven pyroptosis pathway. This study highlights the beneficial impact of bulk material thinning on enhancing ROS generation efficiency and anti‐cancer effects. This work reports on the engineering of atomically thin Bi2O2(OH)(NO3) nanosheets as ROS generator and pyroptosis inducer for sonopiezoelectric cancer therapy through shortening the migration distance of carriers, expanding the specific surface area, and accelerating the charge transfer efficiency.