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

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.

Selective FRET nano probe based on carbon dots and naphthalimide–isatin for the ratiometric detection of peroxynitrite in drug-induced liver injury

“…38–44 However, detection methods based on emission intensities at a single wavelength are not reliable and accurate enough due to the interference from the environment and probe concentrations. 45–50 Ratiometric fluorescent probes designed based on Föster resonance energy transfer (FRET) can avoid these kind of interference to a significant extent. 47,51 Based on non-radiative diploe–dipole interaction, the energy of a fluorophore donor in an excited state can transfer to a fluorophore acceptor in the ground state.…”

Rational design of a near-infrared fluorescent probe for monitoring butyrylcholinesterase activity and its application in development of inhibitors

“…et al proposed a donor-dual-acceptor π-electron cyanine skeleton (QCy7, also termed as TBO) for generation of novel class of Turn-ON NIR probes ( Karton-Lifshin et al, 2011 ). Due to the simple synthesis technique, unique turn-on option, NIR emission, and larger Stokes-shift, TBO has garnered much of attention ( Zhang et al, 2019 ; 2022 ; Chai et al, 2023 ). Following that, numerous TBO-based probes were developed for non-invasive NIR imaging of key biological analytes.…”

Human serum albumin-based supramolecular host–guest boronate probe for enhanced peroxynitrite sensing

“…16,17 The probes developed have achieved the visualization of ONOO − in living cells and tissues, allowing researchers to study ONOO − relevant biological events in real-time. 18 They can also be used to quantify ONOO − levels in biological samples, thus facilitating the diagnosis of diseases associated with ONOO − . Fluorescent probes targeting ONOO − typically consist of a fluorophore that is coupled to a specific chemical moiety that reacts with ONOO.…”