Nanoplatform for renal ischemia-reperfusion injury repair: Modulating macrophage polarization, oxidative stress, and...

Acute kidney injury (AKI) is a common clinical condition characterized by high morbidity and mortality rates, with a notable lack of effective therapeutic drugs. Complex pathological processes-such as oxidative stress overload, aberrant macrophage polarization, mitochondrial dysfunction, and renal tubular epithelial cell apoptosis-contribute to the current absence of effective clinical treatments for AKI. Although mesoporous cerium dioxide nanospheres have been widely applied in various diseases due to their remarkable ROS-scavenging and drug-loading capabilities, their poor targeting ability limits their use in ischemia-reperfusion injury models. To address this, we developed a multifunctional nanoplatform RGD-CeO₂@Que. based on mesoporous hollow cerium dioxide (AhCeO₂). This system achieves targeted accumulation in injured kidneys by binding to integrin αvβ3 receptors, which are overexpressed under oxidative stress. Through the Nrf2/HO-1/GPX4/SOD1 pathway, it alleviates oxidative stress and reduces apoptosis. Moreover, the platform is loaded with the bioactive molecule quercetin to promote mitophagy in renal tubular epithelial cells (HK-2). In vivo studies demonstrated that RGD-CeO₂@Que. improves renal function, ameliorates pathological damage, and reduces inflammatory infiltration in AKI mice. In summary, this integrated nanoplatform combines multiple restorative mechanisms, offering a novel and targeted therapeutic strategy for AKI induced by renal ischemia-reperfusion injury.