Piezoelectric Au-decorated ZnO nanorods: Ultrasound-triggered generation of ROS for piezocatalytic cancer therapy

Nanocatalytic cancer therapy that triggers catalytic reactions to generate cytotoxic reactive oxygen species (ROS) in target cancer cells has recently emerged as an effective therapeutic modality. In this study, piezoelectric, Au-decorated, poly(ethylene glycol)-coated zinc oxide nanorods ([email protected] NRs), a new class of nanoscale piezocatalysts, were developed for efficient cancer treatment via US-triggered piezocatalytic generation of ROS. The detailed piezocatalytic mechanism of [email protected] NRs was also proposed. Under US exposure, thermally excited electrons and holes that are produced in ZnO NRs are separated and accumulated at the surface by piezoelectric polarization, which subsequently catalyzes the generation of ROS for piezocatalytic cancer therapy. Au NPs, as Fenton-like catalysts, were deposited on the surface of the P-ZnO NRs to enhance the piezocatalytic generation of ROS. A pro-oxidant drug, piperlongumine (PL), was loaded into [email protected] NRs to enhance their cancer-specificity and anticancer effects. The variation in piezoelectric potential with respect to the size of the ZnO NRs and the pressure applied by US were calculated using COMSOL Multiphysics®. Under US irradiation, the piezocatalytic [email protected] NRs considerably amplified intracellular ROS levels in MCF-7 human breast cancer cells. PL-loaded [email protected] NRs ([email protected] NRs) revealed efficient and cancer-specific cytotoxicity in MCF-7 cells under US irradiation, thereby confirming effective chemo-piezocatalytic combination cancer therapy. Notably, a single intravenous injection of [email protected] NRs with US exposure significantly suppressed tumor growth without resulting in systemic toxicity in mice. This study demonstrates the feasibility of [email protected] NRs as US-triggered piezocatalytic agents that can selectively and effectively eradicate tumors via chemo-piezocatalytic combination therapy.