Hydrogen sulfide (H
2S), once regarded solely as a highly toxic gas, is now recognized as a crucial signaling molecule in plants, bacteria, and mammals. In humans, H
2S signaling plays a role in numerous physiological and pathological processes, including vasodilation,
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Hydrogen sulfide (H
2S), once regarded solely as a highly toxic gas, is now recognized as a crucial signaling molecule in plants, bacteria, and mammals. In humans, H
2S signaling plays a role in numerous physiological and pathological processes, including vasodilation, neuromodulation, and cytoprotection. To exploit its biological functions and therapeutic potential, a wide range of H
2S-releasing compounds, known as H
2S donors, have been developed. These donors are designed to release H
2S under physiological conditions in a controlled manner. Among them, self-reporting H
2S donors are seen as a particularly innovative class, combining therapeutic delivery with real-time fluorescence-based detection. This dual functionality enables spatiotemporal monitoring of H
2S release in biological environments, eliminating the need for additional sensors or probes that could disrupt cellular homeostasis. This review summarizes recent advancements in self-reporting H
2S donor systems, organizing them based on their activation triggers, such as specific bioanalytes, enzymes, or external stimuli like light. The discussion covers their design strategies, performance in biological applications, and therapeutic potential. Key challenges are also highlighted, including the need for precise control of H
2S release kinetics, accurate signal quantification, and improved biocompatibility. With continued refinement, self-reporting H
2S donors offer great promise for creating multifunctional platforms that seamlessly integrate diagnostic imaging with therapeutic H
2S delivery.
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