Zinc oxide nanoparticles with rich oxygen vacancies to treat fungal keratitis independent of photocatalysis

Fungal keratitis (FK) is a serious infectious corneal disease, accounting for approximately 30%-50% of infectious corneal diseases globally, with a high blinding rate. Due to the lack of low-toxicity and effective ophthalmic Antifungal drugs, new Antifungal treatment strategies must be developed. Zinc oxide nanoparticles (ZnO-NPs) are widely utilized in anti-infective applications due to their low toxicity and potent photocatalytic Antibacterial properties. Here, we synthesized oxygen-vacancy-rich zinc oxide nanoparticles (ZnO-OV) to enhance Antifungal activity independent of photocatalysis, and investigated their potential for treating FK. Oxygen vacancy structures were introduced into ZnO-NPs via the reducing action of NaBH₄. Compared with traditional ZnO-NPs, ZnO-OV had more reactive sites on its surface, good dispersibility, and efficient production of ROS in the dark. In vitro Antifungal experiments showed that ZnO-OV increased the Antifungal rate (40.97% in light and 17.21% in dark), blocked biofilm formation, destroyed hyphal morphology and normal structure. Compared with traditional ZnO-NPs, the improvement in Antifungal activity of ZnO-OV was increased by 6 times under dark environment. Transcriptome analysis of Fungal hyphae indicated that ZnO-OV significantly damaged the cell wall and membrane of A.fumigatus, thereby enhancing its Antifungal activity. In mouse models of FK, ZnO-OV reduced tissue inflammatory damage, neutrophil accumulation, and the expression of inflammatory factors (IL-6, TNF-α, and IL-1β), and showed a stronger curative effect than NATA treatment. These findings highlight ZnO-OV as a novel, photocatalysis-free Antifungal strategy, and that can ameliorate FK.