A near-infrared fluorescence probe for sensing mitochondrial viscosity in cells and mice

Mitochondria play a critical role in providing energy to maintain cellular physiological functions. The viscosity in mitochondria is one of the important indicators of mitochondrial microenvironment. When mitochondrial viscosity increases, it often indicates the occurrence or development of certain diseases. Herein, a series of near-infrared (NIR) fluorescent probes (ZHY-1 ∼ 4) were developed to detect viscosity changes. After screening, we selected ZHY-2 for cellular imaging, since it had the largest fluorescence intensity enhancement (222 times) in response to viscosity compared to the other probes (ZHY-1, ZHY-3, ZHY-4). In addition, ZHY-2 responded to viscosity specifically, and was not affected by pH and other biological species. Also, the probe ZHY-2 had good biocompatibility and mitochondria-targeting ability. It has been applied to measure viscosity changes after stimulation of nystatin and rapamycin. Finally, using probe ZHY-2, we have achieved the real-time fluorescence imaging of viscosity during starvation, as well as in drug-induced liver injury mice.