1. ZIF-8 offers an anti-inflammatory and antifungal strategy for treating Aspergillus fungus keratitis
- Author
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Fu, Xueyun, Tian, Xue, Lin, Jing, Wang, Qian, Gu, Lingwen, Wang, Ziyi, Chi, Menghui, Yu, Bing, Feng, Zhuhui, Liu, Wenyao, Zhang, Lina, Li, Cui, and Zhao, Guiqiu
- Subjects
Quantitative Biology - Tissues and Organs - Abstract
Background: Fungal keratitis is a serious blinding eye disease. Traditional drugs used to treat fungal keratitis commonly have the disadvantages of low bioavailability, poor dispersion, and limited permeability. Purpose: To develop a new drug for the treatment of fungal keratitis with improved bioavailability, dispersion, and permeability. Methods: ZIF-8 was formed by zinc ions and 2-methylimidazole linked by coordination bonds and characterized by SEM, XRD, and Zeta potential. The safety of ZIF-8 on HCEC cells and RAW 264.7 cells was detected by CCK-8. Safety evaluation of ZIF-8 on mice corneal epithelium was conducted using the Driaze corneal toxicity test. The effects of ZIF-8 on fungal growth, biofilm formation, and hyphae structure were detected by MIC, crystal violet staining, PI testing, calcofluor white staining, and SEM. The anti-inflammatory effects of ZIF-8 on RAW 246.7 cells were evaluated by qPCR and Elisa. Clinical score, CFU, HE staining, and immunofluorescence were conducted to verify the therapeutic effect of ZIF-8 on C57BL/6 female mice with fungal keratitis. Elisa confirmed the regulatory effect of ZlF-8 on protein expression of TNF-{\alpha} and IL-6 in the cornea of mice. Results: In vitro, ZIF-8 showed outstanding antifungal effects, including inhibiting the growth of Aspergillus fumigatus, restraining the formation of biofilm, and destroying cell membranes. In vivo, treatment with ZIF-8 reduced corneal fungal load and mitigated neutrophil infiltration in fungal keratitis, which effectively reduced the severity of keratitis in mice and alleviated the infiltration of inflammatory factors in the mouse cornea. In addition, ZIF-8 reduces the inflammatory response by downregulating the expression of pro-inflammatory cytokines TNF-{\alpha}, IL-6, and IL-1\b{eta} after Aspergillus fumigatus infection in vivo and in vitro., Comment: 28 pages, 1 scheme, 8 figures. This work has been submitted to the international journal of nanomedicine for possible publication
- Published
- 2024