#1336

Carbon dots mitigate renal ischemia-reperfusion injury by inhibiting ferroptosis: a targeted and biocompatible strategy for acute kidney injury in transplantation

P. Lei¹, X. Bu¹, G. Gao², S. Wu³, W. Wu², K. Wu^2,1

¹Yulin Hospital of the First Affiliated Hospital of Xi’an Jiaotong University, Department of Urology, Yulin, China
²First Affiliated Hospital of Xi'an Jiaotong University, Department of Urology, Xi'an, China
³First Affiliated Hospital of Xi'an Jiaotong University, Department of Vascular Surgery, Xi'an, China

Introduction:

Renal ischemia-reperfusion (I/R) injury is a primary cause of acute kidney injury (AKI), frequently occurring during kidney transplantation and significantly impacting graft survival and patient outcomes. Ferroptosis, an iron-dependent form of regulated cell death, plays a key role in renal tubular epithelial cell damage during reperfusion. Here, we report the therapeutic potential of carbon dots (C-dots)—a class of ultrasmall, biocompatible nanomaterials—in attenuating I/R-induced AKI by inhibiting ferroptosis.

Material and methods:

A murine model of renal I/R injury was used to simulate clinical transplantation-associated AKI. C-dots (diameter <10 nm), capable of crossing the glomerular filtration barrier and preferentially accumulating in renal tissue, were administered intravenously. Renal function (serum creatinine, BUN), histological changes, and biomarkers of oxidative stress and ferroptosis were evaluated. RNA sequencing was conducted to explore underlying molecular mechanisms. In vivo biodistribution, tissue toxicity, and pharmacokinetics were also assessed to determine safety and translational feasibility.

Results:

C-dots exhibited a favorable pharmacokinetic profile with an in vivo half-life of approximately 43 minutes and no evident toxicity in major organs including the heart, liver, spleen, lung, and kidney. Their renal-targeting capacity enabled efficient delivery to injured tissue. Treatment with C-dots significantly improved renal function (P < 0.001), reduced tubular damage (P < 0.01), and suppressed ferroptosis markers such as lipid peroxidation, 4-HNE accumulation, and mitochondrial dysfunction. Iron overload and ROS levels were also markedly decreased. Transcriptomic analysis confirmed modulation of ferroptosis-related pathways, including downregulation of ACSL4 and restoration of iron/redox homeostasis.