Perfluorocarbon Nanoparticles Loaded with Oxygen Alleviate Acute Kidney Injury via Ameliorating Renal Oxygenation Level

Renal microcirculatory disturbances and tissue hypoxia play a pivotal role in acute kidney injury (AKI) initiation and progression, and addressing renal hypoxia during the acute phase presents a promising therapeutic strategy for preventing AKI or protecting kidney function. In this study, we explored the renal protective potential of perfluorocarbon nanoparticles (PFPs), engineered for superior oxygen-carrying and delivery capacities, in an AKI mouse. Specifically, PFP-treated mice exhibited significant reductions in tubular dilation, necrosis, and brush border loss in renal tubules. Additionally, PFP pretreatment reduced tissue inflammation and fibrosis, as indicated by decreased nuclear factor-kappa B, α-smooth muscle actin, fibronectin, and collagen I expression. Serum creatinine and blood urea nitrogen levels improved, decreasing by 26.9% and 41.7%, respectively. Flow cytometry further showed controlled levels of f4/80⁺ macrophages and CD45⁺ inflammatory markers, with f4/80⁺ macrophages reduced by approximately 31.2% and CD45⁺ inflammatory factors reduced by 40.5%. Metabolomic analyses highlighted PFP's modulation of key metabolic pathways linked to renal recovery, notably up-regulating slc22a19 by 48.3%, a gene encoding a short-chain fatty acid transporter, and down-regulating hyaluronic acid synthesis in renal tissue. These findings are the first to demonstrate that PFPs, as an oxygen carrier, can enhance renal resilience against IR (ischemia-reperfusion)-induced AKI, offering compelling evidence of PFP's clinical potential in AKI management.