Chitosan Oligosaccharide-Functionalized Ruthenium-Curcumin Nanodots for Targeted Therapy of Acute Kidney Injury.

Background: Acute kidney injury (AKI) is a critical clinical syndrome with high morbidity and mortality, primarily driven by mitochondrial oxidative stress and tubular epithelial cell apoptosis. Current antioxidant therapies are limited by poor bioavailability and lack of renal specificity. To address this, we developed a dual-targeting nanomedicine based on ultrasmall chitosan oligosaccharide-functionalized ruthenium-curcumin nanodots (LMWC/Ru-Cur). Methods: Ru-Cur coordination polymer nanodots were synthesized and subsequently coated with low-molecular-weight chitosan (LMWC). The nanoparticles were characterized for size, surface charge, stability, and antioxidant capacity. In vitro studies using HK-2 cells assessed cytocompatibility, cellular uptake, and protection against H Results: The resulting LMWC/Ru-Cur nanodots exhibited uniform size (~7.6 nm), good aqueous stability, and potent broad-spectrum radical scavenging ability. They were efficiently internalized by renal tubular cells via megalin receptor-mediated endocytosis, leading to significantly enhanced renal accumulation. Treatment with LMWC/Ru-Cur attenuated oxidative stress, restored mitochondrial function, reduced apoptosis in injured HK-2 cells, and improved renal function (serum creatinine and blood urea nitrogen), histopathology, and inflammatory cytokine levels in both AKI models, outperforming free curcumin or unmodified Ru-Cur. The nanodots also demonstrated favorable short-term biocompatibility and in vivo biosafety. Conclusion: LMWC/Ru-Cur nanodots represent a promising targeted nanotherapeutic strategy for AKI, integrating passive glomerular filtration with active receptor-mediated tubular delivery to effectively mitigate oxidative stress and mitochondrial damage, thereby preserving renal function. This work provides a rational design for metal-polyphenol based nanomedicines in the treatment of acute organ injury.