A Highly Sensitive and Selective Near-Infrared Fluorescent Probe for Imaging Peroxynitrite in Living Cells and Drug-Induced Liver Injury Mice
Xianzhi Chai, Bohan Li, Chi Chen, Weijian Zhang, Lu-Lu Sun, Hai‐Hao Han, Yafei Zhang, Shasha Sun, Jianming Yang, Junji Zhang, Xiao‐Peng He
Abstract
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.