Tian Yuan, Ye Ziyu, Wang Xunrui, Guan Hantian, Liu Weifeng, Duan Xiaolu, Liu Yang, Zeng Guohua, Liu Hongxing
Guangdong Provincial Key Laboratory of Urological Diseases, Guangdong Engineering Research Center of Urinary Minimally invasive surgery Robot and Intelligent Equipment, Guangzhou Institute of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510120, China.
Beijing Key Laboratory of Materials Utilization of Nonmetallic Minerals and Solid Wastes, National Laboratory of Mineral Materials, School of Materials Science and Technology, China University of Geosciences, Beijing, 100083, P. R. China.
Adv Healthc Mater. 2025 Mar;14(8):e2401574. doi: 10.1002/adhm.202401574. Epub 2024 Aug 22.
There remains a lack of effective drugs to alleviate the kidney stones caused by oxidative stress and inflammatory damage. The MOF-818 nanozyme is utilized to lessen the generation of reactive oxygen species (ROS) effectively, restore the membrane potential of mitochondria, regulate the cell cycle, decrease cell death, hinder the recruitment of macrophages, and mitigate the release of inflammatory factors in macrophages. These effects are attributed to the nanozyme's ability to mimic the enzyme properties of catalase (CAT) and superoxide dismutase (SOD). It is demonstrated that this nanozyme can reduce kidney calcium oxalate crystal deposition by reducing the renal injury caused by high concentration oxalate, upregulate the expression levels of SOD and CAT in tissues, downregulate adhesion proteins and inflammatory factor IL-6 and TNF-α, and promote the polarization of macrophages from M1 to M2 phenotype in the rat model induced by ethylene glycol. Overall, MOF-818 has the potential to effectively suppress oxidative stress and inflammatory harm caused by high levels of oxalate, hence lowering the likelihood of stone formation. MOF-818 nanozyme is also expected to be used as an alternative drug for the treatment of calcium oxalate kidney stones and provide an experimental theoretical basis for the development of new nanomedicines.
目前仍缺乏有效的药物来缓解由氧化应激和炎症损伤引起的肾结石。MOF-818纳米酶可有效减少活性氧（ROS）的产生，恢复线粒体膜电位，调节细胞周期，减少细胞死亡，阻碍巨噬细胞的募集，并减轻巨噬细胞中炎症因子的释放。这些作用归因于该纳米酶模拟过氧化氢酶（CAT）和超氧化物歧化酶（SOD）的酶特性的能力。结果表明，这种纳米酶可通过减轻高浓度草酸盐引起的肾损伤来减少肾草酸钙晶体沉积，上调组织中SOD和CAT的表达水平，下调粘附蛋白以及炎症因子IL-6和TNF-α，并促进乙二醇诱导的大鼠模型中巨噬细胞从M1型向M2型的极化。总体而言，MOF-818有潜力有效抑制高水平草酸盐引起的氧化应激和炎症损伤，从而降低结石形成的可能性。MOF-八18纳米酶也有望用作治疗草酸钙肾结石的替代药物，并为新型纳米药物的开发提供实验理论依据。
