Journal
NANO RESEARCH
Volume 15, Issue 7, Pages 6315-6327Publisher
TSINGHUA UNIV PRESS
DOI: 10.1007/s12274-022-4257-y
Keywords
gallium nanoparticles; acute kidney injury; ischemia-reperfusion injury; iron metabolism; ferroptosis
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Funding
- National Key R&D Program of China [2018YFC2000400]
- Zhejiang Provincial Natural Science Foundation of China [LZ22H050001]
- National Natural Science Foundation of China [81970573, 81670651, 82000637]
- Zhejiang provincial program for the Cultivation of High-level Innovative Health talents
- Medical Health Science and Technology Project of Zhejiang Provincial Health Commission [2020KY538]
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This study synthesized gallic acid-gallium polyvinyl pyrrolidone nanoparticles (GGP NPs) as a potential iron-scavenging agent and demonstrated their good biocompatibility and protective effects in inhibiting ferroptosis. Treatment with GGP NPs significantly ameliorated renal injury and mitochondrial damage, making them a potential candidate for AKI treatment.
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.
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