Ratiometric Detection of H2S in Liver Injury by Activated Two-Wavelength Photoacoustic Imaging

Metformin is commonly used for clinical treatment of type-2 diabetes, but long-term or overdose intake of metformin usually causes selective upregulation of H₂S level in the liver, resulting in liver injury. Therefore, tracking the changes of H₂S content in the liver would contribute to the prevention and diagnosis of liver injury. However, in the literature, there are few reports on ratiometric PA molecular probes for H₂S detection in drug-induced liver injury (DILI). Accordingly, here we developed a H₂S-activated ratiometric PA probe, namely BDP-H₂S, based Aza-BODIPY dye for detecting the H₂S upregulation of metformin-induced liver injury. Due to the intramolecular charge transfer (ICT) effect, BDP-H₂S exhibited a strong PA signal at 770 nm. Following the response to H₂S, its ICT effect was recovered which showed a decrement of PA₇₇₀ and an enhancement of PA₈₄₀. The ratiometric PA signal (PA₈₄₀/PA₇₇₀) showed excellent H₂S selectivity response with a low limit of detection (0.59 μM). Bioimaging experiments demonstrated that the probe has been successfully used for ratiometric PA imaging of H₂S in cells and metformin-induced liver injury in mice. Overall, the designed probe emerges as a powerful tool for noninvasive and accurate imaging of H₂S level and tracking its distribution and variation in liver in-real time.