Visual Diagnosis of Drug-Induced Pulmonary Fibrosis Based on a Mitochondrial Viscosity-Activated Red Fluorescent Probe

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and irreversible fatal disease, the prevalence of which has been increasing in recent years. Nonradiographic and noninvasive early diagnosis of pulmonary fibrosis could improve prognosis but is a formidable challenge. As one of the fundamental microenvironmental parameters, viscosity is relevant to various pathological states, such as acute inflammation. Nevertheless, the potential biological roles of viscosity during the IPF process have been relatively underexplored. To address this issue, herein, we developed a new viscosity-responsive probe (JZ-2), which displayed high sensitivity and selectivity for viscosity, as well as excellent characteristics for targeting mitochondria. JZ-2 was successfully applied to map the changes in mitochondrial viscosity in cells caused by various stimuli, such as nystatin and lipopolysaccharide. Besides, JZ-2 was capable of differentiating cancer cells from normal cells and even tissues. More importantly, JZ-2 has been demonstrated to be sufficiently sensitive for tumor detection and early identification of IPF in vivo, revealing a significant increase in the viscosity of lung fibrosis tissues. Thus, JZ-2 is expected to be a swift and reliable diagnostic modality for the prediction of IPF progression in clinical settings.