Fluorescent Probes for Endogenous Hydrogen Sulfide: Advances and Challenges

Hydrogen sulfide (H₂S), a well-known endogenous biological molecule, is an acidic, colorless gas notorious for its unpleasant rotten-egg smell. Unveiled as an endogenous signaling molecule, H₂S demonstrates significant biological functionalities in various physio-pathological processes. Dysregulation of H₂S expression in biological systems has been implicated in the development of numerous diseases, including cancer. Consequently, precisely sensing H₂S in cells and organisms becomes crucial for understanding fundamental cellular functions. Fluorescent probes have become a potent tool for monitoring H₂S biological activities within complex biological systems. While numerous reviews have explored H₂S sensing and imaging, most have concentrated on exogenous and endogenous detection methods, emphasizing sensing mechanisms and construction. Notably, none have exclusively focused on endogenous H₂S monitoring without introducing an external stimulator, which is essential for in vivo tracking of H₂S in various pathologies and oncology. This review aims to fill this gap by summarizing fluorescent probes designed for detecting endogenous H₂S without the addition of external stimulators, both in vitro and in vivo, from 2014 until 2024. By doing so, we aim to deepen readers' understanding of the biological role of H₂S and provide them with essential biomedical background knowledge for developing H₂S probes that can detect endogenous H₂S without reliance on external stimuli.