Piezo-Mediated Inhibition of Ferroptosis Alleviates Acute Liver Injury

Acute liver injury is closely linked to the pathophysiological cascade effect of iron dysregulation and oxidative stress caused by ferroptosis. Existing monotherapies using iron chelators or antioxidants fail to meet the needs of bidirectional regulation, and lack targeting and specificity. In this study, nanomedicine composed of piezoelectric materials and nanozymewas established for piezo-mediated dual-mode therapy of iron homeostasis regulation and free radical scavenging under localized ultrasound excitation: piezoelectric polarization reduced CeO2 energy barriers and enhanced its superoxide dismutase like enzyme activity through electron injection and orbital hybridization for efficient ROS scavenging; BTO generated holes reduced unstable iron pools by oxidizing divalent iron ions to achieve iron homeostasis; ultimately achieving efficient and high spatiotemporal precision in reversing ferroptosis. BTO@CeO2 achieved antioxidant and iron metabolism reprogramming by regulating ferritinophagy, successfully alleviating drug-induced acute liver injury. This work demonstrates the great potential of piezoelectric-nanozyme synergistic precision treatment of metabolic diseases.