Selenium-Doped Carbon Dots as a Multipronged Nanoplatform to Alleviate Oxidative Stress and Ferroptosis for the Reversal of Acute Kidney Injury

Abstract

Acute kidney injury (AKI) is a life-threatening condition characterized by a rapid decline in the renal function, primarily caused by oxidative stress, inflammation, and ferroptosis. Herein, we present selenium-doped carbon dots (Zt-SeCDs) that integrate antioxidant activity with the controlled release of Zileuton, a 5-lipoxygenase (ALOX5) inhibitor, under high reactive oxygen species (ROS) conditions. This nanoplatform can efficiently deliver Zileuton, leveraging its inherent properties to achieve the targeted prevention and treatment of AKI. In vitro studies have confirmed that Zt-SeCDs efficiently eliminate excessive ROS, prevent ferroptotic cell death, and modulate inflammatory responses by reducing the expression of key pro-inflammatory cytokines. Additionally, Zt-SeCDs regulate ferroptosis through the suppression of ALOX5 and the upregulation of glutathione peroxidase 4 (GPX4) expression. The treatment with Zt-SeCDs significantly improves the kidney function, promotes the regeneration of damaged kidney tissue, and alleviates oxidative stress, inflammatory processes, and ferroptotic cell death. Moreover, monitoring serum indicators and observing renal pathological changes further confirmed the potential of Zt-SeCDs in preventing AKI. Notably, Zt-SeCDs activate the AMPK/FoxO1 signaling pathway, enhancing endogenous antioxidant defenses to protect renal tissue from oxidative damage. This promising nanoplatform not only holds significant promise for the treatment and prevention of AKI, but also aims to facilitate its clinical application.