H 2 O 2 -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 H 2 O 2 , as an important biomarker of DILI, plays a crucial role in the progression of DILI. However, there remains a challenge to develop H 2 O 2 -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 ( IR-990 ) with an acceptor-π-acceptor (A-π-A) skeleton for real-time detection of H 2 O 2 in vivo. In the presence of H 2 O 2 , nonfluorescent probe IR-990 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 H 2 O 2 with high sensitivity and selectivity in vitro (LOD = 0.59 μM) and monitor the behavior of endogenous H 2 O 2 in the HepG2 cell model of DILI for the first time. Notably, probe IR-990 was successfully applied in real-time imaging of endogenous H 2 O 2 generation in the DILI mouse model, showing a high signal-to-background ratio of 11.3/1. We envision that IR-990 holds great potential as a powerful diagnosis tool for real-time visualization of H 2 O 2 in vivo and revealing the mechanism of DILI in the future.