Probing Deep Hydrogen Polysulfides Fluctuations In Vivo by Engineering Activatable Fluorescence Reporters with Second Near-Infrared Window Emission

Deep and comprehensive understanding of the intricate biochemical processes mediated by H2Sn (n ≥ 1), but not H2S, is of paramount importance. A few fluorescent probes have been developed with the intention of addressing this issue. However, there is currently no evidence of any activatable NIR-II fluorescent probes for H2Sn-specific imaging over H2S. In this study, we developed the inaugural H2Sn-activated NIR-II probe for specific and deep imaging of H2Sn through a series of molecular engineering strategies. Strong electron-absorbing moieties enabled the redshift of the emission of the designed reporter, while leaving groups with different dissociation capacities were responsible for modulating the selective and sensitive responsiveness to H2Sn over H2S. By using this activatable specific probe for deep tissue mapping of endogenous H2Sn fluctuations, accurate identification of acute inflammation in animal models was achieved. It is anticipated that the advancement of this activatable NIR-II probe will facilitate a more profound comprehension of the physiological implications of H2Sn.