A lysosomal-targeted and viscosity-ultrasensitive near-infrared fluorescent probe for sensing viscosity in cells and a diabetic mice model

Abstract

Diabetes, as a metabolic disorder, has been implicated in organ dysfunction, often correlated with aberrant changes in viscosity. Lysosomal viscosity serves as an indicator of the lysosome's condition and activity, as it always varies synchronously with the change of lysosome's positioning, structure, and internal constituents. Diabetes, a condition within the metabolic disease category, has the potential to disrupt organ function due to irregular changes in viscosity. Therefore, early and precise diagnosis of diabetes is crucial for the prevention and management of diabetic conditions. Understanding the correlation between viscosity variations and lysosomal changes in vivo is vitally important for researching associated diseases. In this study, we developed Lyso-V, a near-infrared (NIR) fluorescent probe targeting lysosomes, with ultrasensitivity to viscosity changes. This probe, designed with a donor-π-bridge-acceptor (D-π-A) structure, exhibits a significant increase in NIR fluorescence intensity (approximately 690 times) when responding to viscosity, due to a twisted intramolecular charge transfer (TICT) mechanism. Furthermore, the probe designed specifically for lysosomes, enables the detection of changes in lysosomal viscosity as well as autophagy processes. Notably, through the application of this probe, we have detected an increased viscosity within the pathological model of the diabetic mouse. Moreover, Lyso-V was employed to measure the viscosity in diabetic mice. Owing to the multifaceted nature of the Lyso-V probe, it is anticipated to act as a practical and potent resource for deepening our understanding of the pathophysiological aspects of diabetes and aiding in its early detection.