A high signal-to-noise ratio NIR fluorescent probe for viscosity detection in NAFLD diagnosis

Abstract

Viscosity is a critical parameter within the cellular environment, playing a fundamental role in various biochemical processes and the functional integrity of organelles. Abnormal viscosity fluctuations are often linked to conditions such as Non-alcoholic fatty liver disease (NAFLD), diabetes, and neurodegenerative disorders. Thus, monitoring viscosity variations in biological systems is vital for disease-related research. In this study, we have styled and synthesized VFP-4, a near-infrared (NIR) fluorescent probe with a high signal-to-noise ratio (436.4-fold), which demonstrates highly sensitive responsiveness to viscosity changes while remaining unaffected by pH and various interfering substances. Furthermore, VFP-4 was successfully employed in the imaging of viscosity in live cells treated with dexamethasone (DXM) or lipopolysaccharide (LPS), showing precise targeting of lipid droplets (LDs). Notably, due to its NIR emission and exceptional sensitivity to viscosity, VFP-4 can detect real-time viscosity changes in zebrafish and mouse models of NAFLD while exhibiting excellent photostability during imaging. This work holds significant potential for advancing our understanding of cellular processes and developing novel diagnostic and therapeutic strategies by enabling real-time, non-invasive monitoring of intracellular viscosity changes.