Nanomedicines targeting mitochondrial oxidative stress for the treatment of acute kidney injury

Acute kidney injury (AKI) is a highly heterogeneous clinical syndrome with complex pathogenesis, poor outcomes, and no specific pharmacotherapy. Mitochondrial dysfunction and excessive oxidative stress are central to the onset and progression of AKI and have emerged as important therapeutic targets. Conventional antioxidants are limited by modest antioxidant capacity, poor in vivo stability, low bioavailability, and inefficient mitochondrial targeting. Advances in nanotechnology have enabled new inorganic, organic, and bio-derived nanosystems to accumulate at injured renal sites, selectively recognize tubular cells, localize to mitochondria, and efficiently remove excessive reactive oxygen species (ROS) while restoring mitochondrial function, thereby opening new avenues for AKI therapy. This review summarizes the mechanisms by which mitochondrial oxidative stress drives AKI; examines multilevel nanomedicine delivery from the organ to the subcellular scale; categorizes the design principles, mechanisms of action, and therapeutic performance of inorganic, organic, and bio-derived mitochondria-targeted antioxidant nanomedicines; and critically discusses the major barriers and realistic pathways to clinical translation. The review aims to provide a conceptual framework for developing safe and effective targeted nanotherapies for AKI.