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

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Abstract

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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Acknowledgements

This work was supported by grants from the National Key R&D Program of China (No. 2018YFC2000400), Zhejiang Provincial Natural Science Foundation of China (No. LZ22H050001), the National Natural Science Foundation of China (Nos. 81970573, 81670651, and 82000637), Zhejiang provincial program for the Cultivation of High-level Innovative Health talents, and Medical Health Science and Technology Project of Zhejiang Provincial Health Commission (No. 2020KY538).

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  1. Xishao Xie and Yunjing Zhang contributed equally to this work.

Authors and Affiliations

  1. Kidney Disease Center, the First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, 310003, China

    Xishao Xie, Junni Wang, Xi Yao, Qin Zhou, Jianghua Chen & Fei Han

  2. International Institutes of Medicine, the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Jinhua, 322000, China

    Yunjing Zhang, Xinwan Su & Weiqiang Lin

  3. Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, 310029, China

    Yunjing Zhang

  4. Department of Clinical Pharmacy, the First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, 310003, China

    Dou Lv

  5. Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, Hangzhou, 310003, China

    Dou Lv

  6. Department of Nephrology, National Clinical Research Center For Child Health, Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China

    Jianhua Mao

  7. Key Laboratory of Women’s Reproductive Health Research of Zhejiang Province, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China

    Yangyang Li

  8. Cancer Center, Zhejiang University, Hangzhou, 310058, China

    Yangyang Li

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  1. Xishao Xie
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Correspondence to Fei Han, Yangyang Li or Weiqiang Lin.

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

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Xie, X., Zhang, Y., Su, X. et al. Targeting iron metabolism using gallium nanoparticles to suppress ferroptosis and effectively mitigate acute kidney injury. Nano Res. 15, 6315–6327 (2022). https://doi.org/10.1007/s12274-022-4257-y

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