ZIF-90 treats fungal keratitis by promoting macrophage apoptosis and inhibiting inflammatory response

TL;DR

This study demonstrates that ZIF-90, a synthesized metal-organic framework, effectively treats fungal keratitis by disrupting fungal cells and reducing inflammation, showing promise as a novel therapeutic agent.

Contribution

The paper introduces ZIF-90 as a new treatment for fungal keratitis, highlighting its dual antifungal and anti-inflammatory properties with superior biocompatibility.

Findings

ZIF-90 disrupts Aspergillus fumigatus cell structures.

ZIF-90 promotes apoptosis of inflammatory cells.

ZIF-90 shows better biocompatibility than similar compounds.

Abstract

Fungal keratitis is a severe vision-threatening corneal infection with a prognosis influenced by fungal virulence and the host's immune defense mechanisms. The immune system, through its regulation of the inflammatory response, ensures cells and tissues can effectively activate defense mechanisms in response to infection and injury. However, there is still a lack of effective drugs that attenuate fungal virulence while relieving the inflammatory response caused by fungal keratitis. Therefore, finding effective treatments to solve these problems is particularly important. We synthesized ZIF-90 by water-based synthesis and characterized by SEM, XRD etc. In vitro experiments included CCK-8 and ELISA. These evaluations verified the disruptive effects of ZIF-90 on Aspergillus. fumigatus spore adhesion, morphology, cell membrane, and the effect of ZIF-90 on apoptosis. In addition, to investigate whether the metal-ligand zinc and the organic ligand imidazole act as essential factors in ZIF-90, we investigated the in vitro antimicrobial and anti-inflammatory effects of ZIF-8, ZIF-67, and MOF-74 (Zn) by MIC and ELISA experiments. ZIF-90 has therapeutic effects on fungal keratitis, which could break the protective organelles of Aspergillus. fumigatus, such as the cell wall. In addition, ZIF-90 can avoid excessive inflammatory response by promoting apoptosis of inflammatory cells. The results demonstrated that both zinc ions and imidazole possessed antimicrobial and anti-inflammatory effects. In addition, ZIF-90 exhibited better biocompatibility compared to ZIF-8, ZIF-67, and MOF-74 (Zn). ZIF-90 has anti-inflammatory and antifungal effects and preferable biocompatibility, and has great potential for the treatment of fungal keratitis.