Aminophenol - ethylenediamine-based carbon dots as antioxidant nanozymes for multimodal protection against acute kidney injury

Acute kidney injury (AKI) remains a major clinical challenge driven by oxidative stress and inflammation, particularly in ischemia–reperfusion and cisplatin-induced injury. Here, we synthesized aminophenol–ethylenediamine-based carbon dots functionalized with polyethylene glycol (AE-CDs@PEG), exhibiting excellent biocompatibility and strong antioxidant capacity with SOD-like activity exceeding 10,000 U/mg. In vitro, AE-CDs@PEG effectively alleviated oxidative damage, mitochondrial dysfunction, and inflammation in human renal tubular epithelial (HK−2) cells under LPS, H₂O₂, and hypoxia/reoxygenation stress. In vivo, AE-CDs@PEG significantly improved renal function, reduced histological damage, and mitigated oxidative stress in both ischemia–reperfusion injury (IRI)- and cisplatin-induced AKI models. Transcriptomic and 16S rRNA analyses revealed that AE-CDs@PEG modulated key inflammatory pathways and restored gut microbiota homeostasis by enriching Akkermansia and elevating short-chain fatty acids, particularly acetic and butyric acids. These findings highlight AE-CDs@PEG as a promising multi-target antioxidant nanozyme for AKI therapy.