Se/S co-doped onion-derived CDs synergistically treat AKI by alleviating oxidative stress and enhancing iron chelation.

Rhabdomyolysis-induced acute kidney injury (RM-AKI) is a life-threatening clinical condition characterized by excessive myoglobin release, leading to kidney tubular obstruction, oxidative stress, and iron-mediated lipid peroxidation. However, current therapies fail to effectively suppress oxidative stress cascades and lack kidney targeting. Herein, we developed a kidney-targeted nanodrug delivery system with multimodal antioxidant functionality (DFO@SOC) for RM-AKI therapy. Using antioxidant capacity as the decisive screening criterion, Se/S co-doped onion-derived carbon dots (SOC) were identified as the optimal nanocarrier through systematic natural polyphenol precursor selection and heteroatom-doping optimization. SOC exhibited pronounced superoxide dismutase-like and catalase-like activities. The iron chelator deferoxamine (DFO) was subsequently loaded onto SOC, yielding uniformly sized, negatively charged DFO@SOC nanoparticles. In vitro studies demonstrated efficient cellular uptake, robust intracellular scavenging of reactive oxygen species (ROS) and iron ions, and negligible cytotoxicity. In an RM-AKI mouse model, DFO@SOC selectively accumulated in injured kidneys. Notably, Sound Touch Visco-elastography (STVi) and Quantitative Tissue Scattering Coefficient (QTSC) enabled noninvasive and real-time evaluation of therapeutic efficacy with kidney stiffness decreasing significantly from ∼14 to 7 kPa. Combined biochemical and histopathological analyses, DFO@SOC treatment significantly reduced Scr from ∼193.31 to ∼93.82 μmol/L and blood urea nitrogen (BUN) from ∼52.99 to ∼30.68 mmol/L compared to the model group. In summary, the synergistic antioxidant and iron-chelation effects of DFO and SOC, establishing DFO@SOC as a promising nanotherapeutic strategy for RM-AKI.