Role of Azole Drugs in Promoting Fungal Cell Autophagy Revealed by an NIR Fluorescence-Based Theranostic Probe.

ABSTRACT

Autophagy, a widespread degradation system in eukaryotes, plays an important role in maintaining the homeostasis of the cellular environment and the recycling of substances. Optical probes for the tracking of autophagy can be used as an effective tool not only to visualize the autophagy process but also to study autophagy-targeted drugs. Various molecule probes for autophagy of cancer cells emerge but are very limited for that of fungal cells, resulting in the lack of research on antifungal drugs targeting autophagy. To address this issue, we report an azole NIR fluorescence-based theranostic probe AF-1 with antifungal activity that is sensitive to autophagy-associated pH. The unique design of this probe lies in the introduction of both the pH-sensitive fluorophore with a detection range matching the pH range of the autophagy process and the conserved core structural fragment of azole drugs, providing a strategy to investigate the relationship between antifungal drug action and autophagy. As such, AF-1 exhibited excellent spectral properties and was found to target and induce the autophagy of the fungal cell membrane while maintaining moderate antifungal activity. Of note, using this theranostic probe as both a dye and drug, the autophagy process of fungi was visualized in a ratiometric manner, revealing the role of azole antifungal drugs in promoting autophagy to induce fungal cell apoptosis.