Phenylenediamine-Based Carbon Nanodots Alleviate Acute Kidney Injury via Preferential Renal Accumulation and Antioxidant Capacity

As a reactive oxygen species (ROS)-promoted disease, acute kidney injury (AKI) is associated with high mortality and morbidity, but no effective pharmacological treatment is available. Kidney-targeted and ROS-reactive antioxidants are in urgent demand for AKI treatment. A promising nanotechnology-based strategy for targeting renal tubules offers new perspectives for AKI treatment but remains challenging because of the glomerular filtration barrier, which requires ultrasmall-sized therapeutics for penetration and filtration. Here, we fabricated four potential antioxidative carbon nanodots (CNDs) with ultrasmall size. After balancing the antioxidant properties and biocompatibility, m-phenylenediamine-based CNDs (PDA-CNDs) were chosen for further research. PDA-CNDs demonstrated remarkable antioxidant properties for scavenging multiple toxic free radicals, enabling efficient protection of cells under various oxidative stresses in vitro. Moreover, fluorescence imaging revealed that PDA-CNDs preferentially accumulated in the injured kidney of mice with ischemia-reperfusion (IR)-induced AKI. Blood renal function tests and kidney tissue staining revealed the therapeutic efficacy of PDA-CNDs for AKI in both the murine IR-induced AKI model and cisplatin-induced AKI model. Collectively, this is the first study revealing that specific rationally designed CNDs could be a promising pharmacological treatment for AKI induced by ROS.