Mechanism of Curcumin Carbon Dots Alleviating Uranium-Induced Renal Lipid Reprogramming Injury by Targeting the HIF-1α/PPARγ Axis

Uranium-induced nephrotoxicity involves complex mechanisms and lacks therapeutic interventions. This study identifies the HIF-1α/PPARγ axis as a key driver of renal lipid reprogramming and injury following uranium exposure. Using molecular docking, co-immunoprecipitation (Co-IP), and HIF-1α knockdown/knockout models, we confirmed that HIF-1α directly regulates PPARγ expression and downstream lipotoxicity. Curcumin-derived carbon dots (CCDs) were synthesized at temperatures ranging from 120 to 210 °C; those prepared at 210 °C (CCDs-210) exhibited uniform size (<10 nm), and excellent biocompatibility. Carbonization temperature governed cellular uptake: CCDs-210 entered via active endocytosis, while CCDs-120 used passive diffusion. In uranium-exposed HK-2 cells, CCDs-210 scavenged ROS, stabilized mitochondrial membrane potential, and suppressed the HIF-1α/PPARγ axis, reversing lipid dysregulation and improving cell viability. In vivo, CCDs-210 attenuated renal histopathological damage, restored renal function, and conferred multi-organ protection. These findings establish the HIF-1α/PPARγ axis as a central mediator of uranium nephrotoxicity and demonstrate that CCDs-210, by targeting this axis, effectively mitigate oxidative stress, inflammation, and lipid metabolic disruption. This work provides both a mechanistic foundation and a translatable nanotherapeutic strategy for treating uranium-induced kidney injury.