Nanoconfined heterojunctions with enhanced piezoelectricity for amplifying reactive oxygen species storms-triggered tumor ferroptosis-like/apoptosis

Poor separation and rapid recombination of electron-hole pairs hinder the reactive oxygen species (ROS) generation efficiency of sonosensitizers and hampers the efficacy of tumor therapy. To overcome these obstacles, the nanoconfinement-enhanced strategy was proposed to construct polyvinylpyrrolidone-modified ZnO₂ nanomedicines loaded with IrO₂ (IZH) for piezoelectric therapy. Nanoconfinement activates IrO₂ nanoclusters for carrier separation, and the ultrasound current density of IZH (29.4 nA cm⁻²) is 2.9 times that of ZnO₂ (10.3 nA cm⁻²) under the ultrasound irradiation. In addition, the internal electric field between IrO₂ and ZnO₂ accelerates electron directed migration under ultrasound. Interestingly, this strategy augmented ROS generation induces ferroptosis-like/apoptosis with the tumor inhibition rate of 90 %. This study provides an promising nanoplatform to trigger efficient carrier separation for enhancing ROS generation through an iridium-based nanoconfinement piezoelectric sonosensitizer on ferroptosis-like and apoptosis, providing new guidance for exploring candidates for piezoelectric therapy.