H2S is a key chemical mediator that exerts a vital role in diverse physiological and pathological processes. However, in vivo tracking of endogenous H2S generation still remains difficult due to the lack of reliable analytical methods. Herein, we present the first example of activatable photoacoustic probes for real-time imaging of H2S in living mice through the full utilization of the superiority of photoacoustic imaging modality at fine spatial resolution during deep tissue penetration. The designed probe can generate high NIR absorption at 780 nm in the presence of H2S, thus producing a strong photoacoustic signal output in the NIR region. Furthermore, this probe exhibits extremely fast and highly selective responsiveness, good water-solubility and excellent biocompatibility. In light of these outstanding features, this probe realizes the direct photoacoustic trapping of endogenous H2S generation in a HCT116 tumor-bearing mouse model. These preliminary imaging studies show that HCT116 colon tumors exhibit CBS upregulation activity, resulting in an increased rate of H2S generation.

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