Synergetic Chemo‐Piezodynamic Therapy of Osteosarcoma Enabled by Defect‐Driven Lead‐Free Piezoelectrics

Abstract Osteosarcoma (OS) is a lethal malignancy of the bone, jeopardizing the life of an enormous population worldwide. There are grand ongoing challenges to improve overall patient survival. Herein, a synergetic chemo‐piezodynamic therapy by defect‐engineered lead‐free piezoelectric (K,Na)NbO₃ (KNN) is reported, which can generate reactive oxygen species (ROS) to effectively circumvent OS. Significant anti‐tumor effects in human OS cells, and xenograft OS models are observed that almost stop the growth of the tumors after treatment with KNN because of oxygen vacancies‐driven free radical catalysis (namely, the chemodynamic therapy), and those effects are enhanced after introducing ultrasonic vibration enabled by the ultrasound‐triggered piezocatalysis (piezodynamic therapy). Moreover, it is found that KNN induces apoptosis and autophagy of OS cells and shows good histocompatibility on evaluation in mouse models, which has no killing effect on normal cells and no toxic effects on organs in vivo. Both in vitro cellular level evaluation and in vivo OS xenograft assessment have demonstrated that injectable KNN nanocrystals induce cytotoxicity and tumor eradication by the synergy of chemo‐piezocatalytic effects. This study opens an avenue for customized design of high‐tech nanocatalysts by integrating synergetic catalytic effects for therapeutic applications in tumor healthcare.