A Sensitive Fluorescent Probe for Tracking Viscosity Changes in the Mitochondria Under Physiological and Pathological...

Mitochondrial viscosity is a key microenvironmental parameter regulating its function, and its dysregulation is associated with various diseases. However, achieving specific and dynamic monitoring of mitochondrial viscosity remains challenging. To address this, we developed a novel near-infrared fluorescent probe, FTZ-BTZ, based on a twisted intramolecular charge transfer mechanism. The probe demonstrates high sensitivity (R² = 0.9906), excellent selectivity, good stability, and low cytotoxicity in viscosity detection. Colocalization imaging confirmed its precise mitochondrial targeting capability, with a Pearson's coefficient of 0.9052. Using this probe, we successfully achieved real-time, in situ visualization of dynamic changes in mitochondrial viscosity within living cells. These changes were induced by various pharmacological stimuli, including lipopolysaccharide, dexamethasone, nystatin, and monensin. Specifically, we established the concentration-dependent response of mitochondrial viscosity to monensin. Further in vivo experiments showed that FTZ-BTZ can effectively distinguish viscosity gradients induced by different drug stimulations in mouse models. The FTZ-BTZ probe developed in this work provides a high-performance molecular tool for real-time investigation of mitochondrial viscosity-related physiological and pathological processes at the subcellular level.