Targeting iron metabolism using gallium nanoparticles to suppress ferroptosis and effectively mitigate acute kidney injury

Ferroptosis plays a critical pathophysiological role in several types of acute kidney injury (AKI). The development of nanomaterials targeting iron metabolism and ferroptosis is a promising approach for AKI treatment. Herein, we synthesized gallic acid-gallium polyvinyl pyrrolidone nanoparticles (GGP NPs) as a potential iron-scavenging agent because of their nearly ionic radius and chemical similarity with iron. The results indicated that GGP NPs accumulated in tubular epithelial cells and showed good biocompatibility. GGP NPs significantly inhibited cisplatin (CP)-induced ferroptosis in HK-2 cells by reducing the accumulation of intracellular free iron and mitochondrial dysfunction, and suppressing the perturbations of ferroptosis processes, including lipid peroxidation, nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione (GSH) levels, glutathione peroxidase 4 (GPX4) activity, and ferritinophagy. An in vivo study demonstrated that treatment with GGP NPs significantly ameliorated the renal tubular injury and mitochondrial damage induced by CP treatment or ischemia-reperfusion injury. Our study suggests that GGP NPs may be an effective and promising candidate for AKI treatment and enable potential clinical translation.