Rational design of dual ratiometric photoacoustic and fluorescent probe for reliable imaging and quantitative detection of endogenous CO during drug-induced liver injury and repair

Carbon monoxide (CO) is an essential gaseous signaling molecule and strongly associated with many physiological and pathological processes. The study of CO chemistry in biology remains challenging, primarily due to limitations in available tools for quantitative detection of the CO fluctuations in vivo. Photoacoustic/fluorescent (PA/FL) dual-mode imaging is a vital tool for in vivo study which has complementary advantages from two modalities. To our knowledge, there are currently no PA/FL dual ratiometric probes to visualize CO in live animals. In this work, we reported the first dual ratiometric PA/FL probe DOP-CO for reliable imaging and quantitative detection of CO based on a novel “Atom Surgery” strategy. As expected, probe DOP-CO was successfully applied to ratiometric imaging of exogenous and endogenous CO release behavior in HepG2 cells. Notably, tail vein injection of DOP-CO resulted in liver-enrichment of mice and the endogenous CO fluctuations in the liver triggered by liver injury and liver repair, respectively, was confirmed by PA/FL dual-modality ratiometric imaging. More importantly, the dual ratiometric probe prepared in this study not only contributes to gain insight into the relationship between CO fluctuations and liver injury, but also provides a promising tool to investigate more CO-mediated biological processes. • A novel “Atom Surgery” strategy was employed for design dual ratiometric FL and PA CO probes. • DOP-CO was prepared as the first dual ratiometric PA/FL probe for quantitative detection CO during liver injury and repair. • The probe DOP-CO displayed outstanding dual ratiometric FL/PA signals towards CO release.