Rosmarinic acid-cerium nanocatalysts enable oxygenation-enhanced ROS neutralization and PET imaging-guided therapy for acute kidney injury.

Abstract

Acute kidney injury (AKI) is driven by a vicious interplay among excessive reactive oxygen species (ROS) accumulation and persistent renal hypoxia, which collectively disrupt redox homeostasis and exacerbate tubular injury. However, current therapeutic strategies primarily provide supportive care and fail to simultaneously modulate these interconnected pathological stressors. Herein, we report a cerium-doped rosmarinic acid nanosystem (RA/Ce NPs) formed via self-polymerization that catalytically eliminates ROS while simultaneously generating oxygen to reprogram the pathological renal microenvironment. The ultrasmall RA/Ce NPs enable efficient chelator-free ⁸⁹Zr radiolabeling for positron emission tomography (PET) imaging. Redox-switchable Ce³⁺/Ce⁴⁺ centers confer robust catalytic activity and ROS-responsive biodegradation, ensuring potent antioxidation with safe clearance. RA/Ce NPs suppress intracellular ROS, preserve mitochondrial membrane potential, and protect against oxidative injury in vitro. In rhabdomyolysis-induced AKI mice, PET imaging reveals pronounced renal accumulation, while treatment markedly alleviates tubular damage, oxidative stress and hypoxia, leading to restored renal function with excellent biocompatibility. This work presents a natural-product-derived catalytic nanoplatform integrating antioxidation, oxygenation, imaging and biodegradability, offering a promising strategy for precision therapy of AKI.