4.8 Article

A Highly Sensitive and Selective Near-Infrared Fluorescent Probe for Imaging Peroxynitrite in Living Cells and Drug-Induced Liver Injury Mice

Journal

ANALYTICAL CHEMISTRY
Volume 95, Issue 13, Pages 5747-5753

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.3c00007

Keywords

-

Ask authors/readers for more resources

Drug-induced liver injury (DILI) is a clinical issue associated with many commercial drugs, and traditional methods cannot monitor the dynamic changes in peroxynitrite (ONOO-) levels during DILI in real time. Therefore, the development of ONOO--activated near-infrared (NIR) fluorescent probes with high sensitivity and selectivity is crucial for early diagnosis of DILI.
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 pi-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 pi- electron system and similar to 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.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.8
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available