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 H₂S_n (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 H₂S_n-specific imaging over H₂S. In this study, we developed the inaugural H₂S_n-activated NIR-II probe for specific and deep imaging of H₂S_n 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 H₂S_n over H₂S. By using this activatable specific probe for deep tissue mapping of endogenous H₂S_n 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 H₂S_n.