HO-Activated NIR-II Fluorescent Probe with a Large Stokes Shift for High-Contrast Imaging in Drug-Induced Liver Injury Mice.

Drug-induced liver injury (DILI) is the most common clinical adverse drug reaction, which is closely associated with the oxidative stress caused by overproduced reactive oxygen species. Hepatic HO, as an important biomarker of DILI, plays a crucial role in the progression of DILI. However, there remains a challenge to develop HO-activatable second near-infrared (NIR-II, 1000-1700 nm) small molecular probes with both a large Stokes shift and a long emission wavelength beyond 950 nm. Herein, we developed an activatable NIR-II fluorescent probe () with an acceptor-π-acceptor (A-π-A) skeleton for real-time detection of HO in vivo. In the presence of HO, nonfluorescent probe was successfully unlocked by generating a donor-π-acceptor (D-π-A) structure and switched on intense NIR-II fluorescence, exhibiting a peak emission wavelength at 990 nm and a large Stokes shift of 200 nm. Moreover, it was able to detect HO with high sensitivity and selectivity in vitro (LOD = 0.59 μM) and monitor the behavior of endogenous HO in the HepG2 cell model of DILI for the first time. Notably, probe was successfully applied in real-time imaging of endogenous HO generation in the DILI mouse model, showing a high signal-to-background ratio of 11.3/1. We envision that holds great potential as a powerful diagnosis tool for real-time visualization of HO in vivo and revealing the mechanism of DILI in the future.