Reactive Oxygen Species-Scavenging Mesoporous Poly(tannic acid) Nanospheres Alleviate Acute Kidney Injury by Inhibiting Ferroptosis

Abstract

Acute kidney injury (AKI), predominantly associated with the excess production of endogenous ROS, is a serious renal dysfunction syndrome. Ferroptosis characterized by iron-dependent regulated cell death has significant involvement in AKI pathogenesis. As symptomatic treatment of AKI remains clinically limited, a new class of effective therapies has emerged, which is referred to as nanozyme. In our research, a natural mesoporous poly(tannic acid) nanosphere (referred to as PTA) was developed that can successfully mimic the activity of superoxide dismutase (SOD) by Mussel-inspired interface deposition strategy, for effective ROS scavenging and thus inhibition of ferroptosis to attenuate AKI. As anticipated, PTA mitigated oxidative stress and inhibited ferroptosis, as opposed to other modes of cell death such as pyroptosis or necrosis. Furthermore, PTA exhibited favorable biocompatibility and safeguarded the kidney against ferroptosis by enhancing the expression of SLC7a11/glutathione peroxidase 4(GPX4) and Nrf2/HO-1, while reducing the levels of ACSL4 protein in the ischemia and reperfusion injury (IRI)-induced AKI model. Moreover, PTA effectively suppressed aberrant expression of inflammatory factors. Overall, this study introduced antioxidative nanozymes in the form of mesoporous polyphenol nanospheres, showcasing exceptional therapeutic efficacy in addressing ROS-related diseases. This novel approach holds promise for clinical AKI treatment and broadens the scope of biomedical applications for nanozymes.