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

Hydrogen persulfide (H₂S₂) plays a significant role in redox biology and signal transduction; therefore, quantitative visualization of H₂S₂ in the deep tissue of living organisms is essential for obtaining reliable information about relevant pathophysiological processes directly. However, currently reported H₂S₂ 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 H₂S₂-mediated dithiole formation reaction. Based on this reaction, we construct the first NIR-II fluorescence (FL) and photoacoustic (PA) dual-ratiometric probe (NIR-II-H₂S₂) for quantitatively visualizing H₂S₂ in vivo. This probe shows dual-ratiometric NIR-II fluorescence (I₈₄₀/I₁₀₀₀, 107-fold) and photoacoustic (PA₈₀₀/PA₉₀₀, 6.5-fold) responses towards Na₂S₂ 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 H₂S₂ levels in the liver-injury mouse models induced by lipopolysaccharides or metformin drugs. Overall, this study not only presents a promising tool for H₂S₂-related pathological research, but also provides a unique recognition site that may be generalized for designing more useful H₂S₂ imaging agents in the future.