Engineering a highly selective probe for ratiometric imaging of H2Sn and revealing its signaling pathway in fatty liver disease

Hydrogen polysulfides (H₂S_n, n > 1) have continuously been proved to act as important signal mediators in many physiological processes. However, the physiological role of H₂S_n and their signaling pathways in complex diseases, such as the most common liver disease, nonalcoholic fatty liver disease (NAFLD), have not been elucidated due to lack of suitable tools for selective detection of intracellular H₂S_n. Herein, we adopted a general and practical strategy including recognition site screening, construction of a ratiometric probe and self-assembly of nanoparticles, to significantly improve the probes'' selectivity, photostability and biocompatibility. The ratiometric probe PPG-Np-RhPhCO selectively responds to H₂S_n, avoiding interaction with biothiol and persulfide. Moreover, this probe was applied to image H₂S_n in NAFLD for the first time and reveal the H₂S_n generation pathways in the cell model of drug-treated NAFLD. The pathway of H₂S_n revealed by PPG-Np-RhPhCO provides significant insights into the roles of H₂S_n in NAFLD and future drug development.

A highly selective probe (PPG-Np-RhPhCO) used for revealing the intracellular H₂S_n signaling pathways in a nonalcoholic fatty liver disease (NAFLD) model.