Tetrahedral DNA Nanostructures Inhibit Ferroptosis and Apoptosis in Cisplatin-induced Renal Injury

Abstract

Acute kidney injury (AKI) is the most serious adverse reaction during cisplatin chemotherapy, which limits the drug's clinical effects. Therefore, effective strategies for protective therapy need to be developed. In the current study, we verified that tetrahedral DNA nanostructures (TDNs), promising DNA nano biomaterials, played protective roles against cisplatin-induced death of renal tubular cells. Herein, we observed that TDNs decreased the generation of lipid reactive oxygen species (ROS), restored the down-regulation of glutathione peroxidase 4 (GPX4), and hence inhibited ferroptosis induced by RSL3, a typical inducer of ferroptosis. In addition, we proved that TDNs attenuated cisplatin-induced ferroptosis by reversing the down-regulation of GPX4 and attenuated apoptosis induced by cisplatin via reducing the cleavage of poly(ADP-ribose) polymerase (PARP). Taking this all into account, our investigation suggested the potential of TDNs for cisplatin-induced AKI therapy.