An Aggregation-induced Emission Probe to Detect the Viscosity Change in Lipid Droplets during Ferroptosis

Ferroptosis is a recently identified form of cell death characterized by iron-dependent lipid peroxidation. Understanding the effects of lipid peroxidation on cellular processes during ferroptosis requires insights into lipid droplets (LDs) and their viscosity changes. To gain further insights into the intricacies of ferroptosis, it is crucial to have a fluorescent probe that targets LDs and responds to changes in viscosity. In this study, we introduce a novel LD-targeting viscosity fluorescent probe named TQE, based on the principles of aggregation-induced emission (AIE). The probe displayed AIE characteristics in tetrahydrofuran, possessing a partition coefficient (logP) of 5.87. With increased viscosity, intramolecular rotation was restricted, leading to a remarkable 3.3-fold enhancement in emission. Notably, TQE exhibited robust resistance to photo-bleaching during cellular imaging, maintaining approximately 75% of its emission intensity even after 30 min of laser irradiation. Importantly, the AIEgen could not generate hydroxyl radicals when exposed to light for up to 3 h, suggesting the low photo-toxicity of TQE to cells. Leveraging these properties, we successfully employed the probe for fluorescent imaging of the viscosity change in LDs during ferroptosis.