A Mn 3 O 4 -based antioxidant nanoplatform loaded with Tacrolimus to ameliorate chronic kidney disease by reducing inflammation and oxidative stress

Abstract Chronic kidney disease (CKD) is one of the most common diseases in the world and an important public health problem that endangers human health. Its pathogenesis is related to the accumulation of excessive ROS in cells. In this study, an ultra-small nanopreparations (NPs) called C-Mn3O4@Tac was provided, which is prepared using citric acid-functionalized Mn3O4 NPs loaded with tacrolimus. This innovative formulation design takes advantage of the ROS clearance ability of Mn3O4 NPs that mimics enzymatic activity in a dark environment and the immunosuppressive capacity of tacrolimus, and enables targeted accumulation in the renal region and sustained drug release through enhanced permeability and retention (EPR) effect. It not only avoids the side effects caused by high-dose drugs or sudden release, but also prolongs the dosing cycle and improves the efficacy to a certain extent. C-Mn3O4@Tac protects the structural and functional integrity of mitochondria from oxidative damage, removes excess ROS in cells to maintain cellular redox homeostasis, inhibits the overexpression of pro-inflammatory cytokines to restore kidney function and maintain normal kidney structure by reducing inflammation and regulating antioxidant stress pathways. This unique working mechanism of ultra-small redox nano-platform with the ability to reduce inflammation and regulate antioxidative stress provides a potentially more effective treatment for CKD patients. This two-pronged treatment strategy also provides new strategies for the treatment of CKD and demonstrates its great potential for clinical translational application.