Dual-site fluorescent sensor for tracking lysosomal ATP and H2S during liver injury

[Display omitted] •The first dual-site fluorescent sensor RDNA-1 for the detection of ATP and H2S.•It allowed highly selective and sensitive detection of ATP/H2S levels in vitro.•The fluctuation of ATP/H2S was accurately firstly monitored during liver injury.•It offered a new tool to study the relationship between ATP/H2S and liver injury. The liver is a vital organ and is involved in many important bodily functions. The liver injury can cause liver disease and seriously threaten human health. The ability to visualize evidence of liver damage in hepatic cells is lacking, and this evidence would indicate changes in the degradation function of lysosomes. Here, we rationally designed a dual-site fluorescent sensor called RDNA-1 to track adenosine triphosphate (ATP) and hydrogen sulfide (H2S) in lysosomes with rhodamine 6G and 1,8-naphthalimide hybrid fluorophores. RDNA-1 exhibited an excellent selectivity, high sensitivity and fast response time toward ATP and H2S in vitro. Additionally, cell imaging results showed that RDNA-1 can be specifically localized in lysosomes to track ATP and H2S. RDNA-1 was successfully employed to detect changes in the ATP and H2S levels during liver injury in real time. In addition, we thoroughly explored the function of H2S as a potential drug for repairing injured liver cells. Importantly, RDNA-1 successfully enabled the in vivo imaging of zebrafish. Therefore, RDNA-1 provides a new approach to study the physiological mechanisms of liver injury, and this is beneficial for the early diagnosis and treatment of liver-related diseases. We believe that the multifunctional sensor can also be applied to track lysosomal ATP and H2S in other disease processes.