Drug-induced liver injury (DILI) is a major clinical
issue associated
with the majority of commercial drugs. During DILI, the peroxynitrite
(ONOO–) level is upregulated in the liver. However,
traditional methods are unable to timely monitor the dynamic changes
of the ONOO– level during DILI in vivo. Therefore, ONOO–-activated near-infrared (NIR)
fluorescent probes with high sensitivity and selectivity are key to
the early diagnosis of DILI in situ. Herein, we report
a novel ONOO–-responsive NIR fluorescent probe, QCy7-DP, which incorporates a donor-dual-acceptor π-electron
cyanine skeleton with diphenyl phosphinate. The ONOO–-mediated highly selective hydrolytic cleavage via an addition-elimination
pathway of diphenyl phosphinate produced the deprotonated form of QCy7 in physiological conditions with a distinctive extended
conjugated π-electron system and ∼200-fold enhancement
in NIR fluorescence emission at 710 nm. Moreover, the probe QCy7-DP was successfully used for the imaging of the endogenous
and exogenous ONOO– concentration changes in living
cells. Importantly, in vivo fluorescence imaging
tests demonstrated that the probe can effectively detect the endogenous
generation of ONOO– in an acetaminophen (APAP)-induced
liver injury mouse model. This study provides insight into the design
of highly selective NIR fluorescent probes suitable for spatiotemporal
monitoring of ONOO– under different pathological
conditions.