NIR-II Fluorescence/Photoacoustic Dual Ratiometric Probes with Unique Recognition Site for Quantitatively Visualizing HS in Vivo

Hydrogen persulfide (HS) plays a significant role in redox biology and signal transduction; therefore, quantitative visualization of HS in the deep tissue of living organisms is essential for obtaining reliable information about relevant pathophysiological processes directly. However, currently reported HS probes are unsuitable for this purpose because of their poor selectivity for many polysulfide species or their short wavelength, which hinders precise imaging in deep tissues. Herein, for the first time, we report a unique HS-mediated dithiole formation reaction. Based on this reaction, we construct the first NIR-II fluorescence (FL) and photoacoustic (PA) dual-ratiometric probe (NIR-II-HS) for quantitatively visualizing HS in vivo. This probe shows dual-ratiometric NIR-II fluorescence (I/I, 107-fold) and photoacoustic (PA/PA, 6.5-fold) responses towards NaS species with high specificity, excellent sensitivity (1.8 nM), improved water solubility, and deep-tissue penetration. More importantly, using NIR-II dual-ratiometric FL/PA imaging, we successfully demonstrated that the probe could be used to accurately quantify the fluctuating HS levels in the liver-injury mouse models induced by lipopolysaccharides or metformin drugs. Overall, this study not only presents a promising tool for HS-related pathological research, but also provides a unique recognition site that may be generalized for designing more useful HS imaging agents in the future.