Redox nanodrugs alleviate chronic kidney disease by reducing inflammation and regulating ROS.

Abstract

Immune-mediated glomerular diseases lead to chronic kidney disease (CKD), primarily through mechanisms such as immune cell overactivation, mitochondrial dysfunction and imbalance of reactive oxygen species (ROS). We have developed an ultra-small nanodrug composed of Mn₃O₄ nanoparticles which is functionalized with biocompatible ligand citrate (C-Mn₃O₄ NPs) to maintain cellular redox balance in an animal model of oxidative injury. Furthermore, this ultra-small nanodrug, loaded with tacrolimus (Tac), regulated the activity of immune cells. We established a doxorubicin (DOX)-induced CKD model in SD rats using conditions of oxidative distress. The results demonstrate the ROS scavenging capability of Mn₃O₄ NPs, which mimics enzymatic activity, and the immunosuppressive effect of tacrolimus. This combination promotes targeted accumulation in the renal region with sustained drug release through the enhanced permeability and retention (EPR) effect. Tac@C-Mn₃O₄ protects the structural and functional integrity of mitochondria from oxidative damage while eliminating excess ROS to maintain cellular redox homeostasis, thereby suppressing the overexpression of pro-inflammatory cytokines to restore kidney function and preserve a normal kidney structure, reducing inflammation and regulating antioxidant stress pathways. This dual-pronged treatment strategy also provides novel strategies for CKD management and demonstrates substantial potential for clinical translational application.