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MOF-818 Nanozyme Suppresses Calcium Oxalate Kidney Stones by Alleviating Oxidative Stress and Inflammatory Injury
Summary:
The authors from the Guangdong Provincial Key Laboratory of Urological Diseases developed a MOF-818 nanozyme with antioxidant and anti-inflammatory properties, achieving significant results in the prevention and treatment of calcium oxalate kidney stones.
Background:
1. Kidney stones, particularly calcium oxalate stones, are a common urological disease with increasing incidence and recurrence rates. Previous treatments include drugs like hydrochlorothiazide and potassium citrate, but they often cause notable adverse effects and lack long-term efficacy. There is a need for more effective and safer therapeutic options.
2. The authors proposed using MOF-818 nanozyme, which mimics the enzyme properties of catalase (CAT) and superoxide dismutase (SOD), to alleviate oxidative stress and inflammatory damage caused by high levels of oxalate, thereby suppressing kidney stone formation.
Research Content:
1. Synthesis:
The authors synthesized MOF-818 based on previous research, using a self-assembly method with Cu(NO₃)₂·3H₂O, ZrOCl₂·8H₂O, and H₂PyC as precursors. The synthesis involved dissolving the precursors in DMF, adding trifluoroacetic acid, and heating the mixture at 100°C for 8 hours.
2. Characterizations:
1) BET analysis showed that MOF-818 had a Brunauer–Emmett–Teller surface area of 535.6 m² g⁻¹ and a pore size of 2.50 nm.
2) SEM/TEM tests revealed that MOF-818 had an octahedral structure with an average diameter of 220 nm.
3) XPS confirmed the presence of Cu²⁺ and Zr in the material, and XRD patterns matched the simulated standard diffraction peaks.
3. Application:
In vitro experiments demonstrated that MOF-818 could protect renal tubular epithelial cells (HK-2) from oxidative damage caused by high-concentration oxalate, restore mitochondrial membrane potential, regulate the cell cycle, and reduce macrophage recruitment and inflammatory factor release. In vivo experiments using a rat model induced by ethylene glycol showed that MOF-818 could alleviate renal injury, downregulate adhesion proteins and inflammatory factors (TNF-α and IL-6), and promote macrophage polarization from M1 to M2 phenotype, ultimately reducing calcium oxalate crystal deposition.
4. Mechanism:
The study suggested that MOF-818 exerted its therapeutic effects by alleviating oxidative stress and inflammatory damage. High-throughput sequencing revealed that MOF-818 downregulated the expression of cytokine CSF2, which is involved in macrophage polarization and inflammatory responses. The nanozyme's ability to scavenge ROS and modify the oxidative stress microenvironment contributed to its anti-inflammatory and anti-stone effects.
Outlook:
This research provides an experimental basis for the development of MOF-818 as a novel nanomedicine for the treatment of calcium oxalate kidney stones. The findings highlight the potential of MOF-818 as an effective and safe alternative to traditional drugs, offering a new strategy for the prevention and treatment of kidney stones.
MOF-818 Nanozyme Suppresses Calcium Oxalate Kidney Stones by Alleviating Oxidative Stress and Inflammatory Injury
Authors: Yuan Tian, Ziyu Ye, Xunrui Wang, Hantian Guan, Weifeng Liu, Xiaolu Duan, Yang Liu, Guohua Zeng, Hongxing Liu
DOI: 10.1002/adhm.202401574
Link: https://onlinelibrary.wiley.com/doi/10.1002/adhm.202401574
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