A mitochondrial-targeted near-infrared fluorescent probe for visualizing the fluctuation of hypochlorite acid in idiopathic pulmonary fibrosis mice

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic inflammatory disease destroying lungs irreversibly with high mortality rates. There are challenges in diagnosing IPF and treating it at an early stage. Mounting evidence suggests that hypochlorous acid (HClO) can help in diagnosing inflammation and relevant conditions. Pulmonary fibrosis is linked to the mitochondrial oxidative stress where excessive HClO production is a key molecular mechanism. Measuring mitochondrial HClO levels assists in the investigations of how the mitochondrial oxidative stress affects IPF. Herein, NIR-PTZ-HClO was developed and optimized as a probe for detecting fluctuations in HClO concentrations of cells and mice models through near-infrared (NIR) fluorescence. The probe featured large Stokes shift of 150 nm, NIR turn-on signal at 650 nm, high sensitivity (45-fold) and quick HClO detection (2 s). The probe is selective for HClO in the presence of range of other analytes. NIR-PTZ-HClO visualized both endogenous and exogenous HClO in living cells (RAW264.7, H460 and A549). The probe monitored HClO in mice models with IPF and moreover the HClO profile could be tracked during the IPF process. The probe also detected precipitous decrease in HClO levels in IPF mice treated with OFEV. NIR-PTZ-HClO probe has thus the potential for earlier diagnosis of lung fibrosis, thereby improving the treatment efficacy.