Targeting iron metabolism using gallium nanoparticles to suppress ferroptosis and effectively mitigate acute kidney injury
Targeting iron metabolism using gallium nanoparticles to suppress ferroptosis and effectively mitigate acute kidney injury
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DOI：
10.1007/s12274-022-4257-y
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发表时间：
2022-05
期刊：
影响因子：
9.9
通讯作者：
Xi-shao Xie;Yunjing Zhang;Xinwan Su;Junni Wang;X. Yao;Dou Lv;Qin Zhou;Jianhua Mao;Jianghua C
中科院分区：
文献类型：
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作者：
Xi-shao Xie;Yunjing Zhang;Xinwan Su;Junni Wang;X. Yao;Dou Lv;Qin Zhou;Jianhua Mao;Jianghua C
铁凋亡在几种类型的急性肾损伤（阿基）中起着关键的病理生理作用。靶向铁代谢和铁凋亡的纳米材料的开发是阿基治疗的一种有前途的方法。在此，我们合成了没食子酸镓聚乙烯吡咯烷酮纳米粒子（GGP NPs）作为一个潜在的铁清除剂，因为它们接近的离子半径和化学相似的铁。结果表明，GGP纳米粒在肾小管上皮细胞中积累，并显示出良好的生物相容性。GGP NPs通过减少细胞内游离铁的积累和线粒体功能障碍，并抑制铁凋亡过程的扰动，包括脂质过氧化、烟酰胺腺嘌呤二核苷酸磷酸（NADPH）和谷胱甘肽（GSH）水平、谷胱甘肽过氧化物酶4（GPX 4）活性和铁蛋白吞噬，显著抑制顺铂（CP）诱导的HK-2细胞铁凋亡。体内研究表明，GGP NPs治疗显著改善CP治疗或缺血再灌注损伤引起的肾小管损伤和线粒体损伤。我们的研究表明，GGP NPs可能是治疗阿基的有效和有前途的候选药物，并能够实现潜在的临床转化。
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. Anin vivostudy 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.