Zeolitic Imidazolate Framework-8 offers an anti-inflammatory and antifungal method in the treatment of Aspergillus fungus keratitis in vitro and in vivo

TL;DR

This study introduces Zeolitic Imidazolate Framework-8 (ZIF-8) as a novel anti-inflammatory and antifungal agent for treating Aspergillus fungus keratitis, demonstrating its effectiveness both in vitro and in vivo.

Contribution

The paper presents ZIF-8 as a new therapeutic approach with improved bioavailability and permeability for fungal keratitis treatment, showing significant anti-inflammatory and antifungal effects.

Findings

ZIF-8 reduces fungal load in infected corneas.

ZIF-8 downregulates pro-inflammatory cytokines.

ZIF-8 alleviates severity of keratitis in mice.

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 method for the treatment of fungal keratitis with improved bioavailability, dispersion, and permeability. Purpose: To develop a new method for the treatment of fungal keratitis with improved bioavailability, dispersion, and permeability. Methods: Zeolitic Imidazolate Framework-8 (ZIF-8) was formed by zinc ions and 2-methylimidazole linked by coordination bonds and characterized by Scanning electron microscopy (SEM), X-ray diffraction (XRD), and Zeta potential. The safety of ZIF-8 on HCECs and RAW 264.7 cells was detected by Cell Counting Kit-8 (CCK-8). The anti-inflammatory effects of ZIF-8 on RAW 246.7 cells were evaluated by Quantitative Real-Time PCR Experiments (qPCR) and Enzyme-linked immunosorbent assay (ELISA). Clinical score, Colony-Forming Units (CFU). 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. Conclusion: ZIF-8 has a significant anti-inflammatory and antifungal effect, which provides a new solution for the treatment of fungal keratitis.