Construction of a novel mitochondria-targeted near-infrared (NIR) probe for detection of viscosity changes in cancer cells ferroptosis process

Mitochondria, as an important organelle in cells, play an important role in the production of adenosine triphosphate (ATP) and cell signal transduction, as well as control of the cell cycle and growth. Abnormal viscosity is a pivotal factor for indicating mitochondrial dysfunction. In addition, abnormal changes in mitochondrial viscosity have been confirmed to be closely related to many diseases and malfunctions, such as cell malignancy, atherosclerosis, diabetes, and Alzheimer's disease. Therefore, the development of mitochondrial viscosity response probe and its application in mitochondrial viscosity measurement are considered as a new tool to understand diseases. So far, most of the fluorescent probes used to detect mitochondrial viscosity have emission wavelengths in the visible region, making them less penetrable to tissue. In this work, we report a novel near-infrared fluorescent probe (MN-V) for the detection of mitochondrial viscosity in live cells, which exhibited near infrared emission (795 nm) and high sensitivity towards viscosity changes. The fluorescence intensity of the probe at 795 nm has a 37 times increase from pure PBS solution to glycerol. There was a linear relationship between the fluorescence intensity and the media viscosity. The probe MN-V was applicable to detection of the viscosity changes in living cells and zebrafish. Most importantly, with the probe we found that during cancer cells ferroptosis process was accompanied by an increase in mitochondrial viscosity.

Automated summary

Mitochondria play a vital role in cellular functions and abnormal viscosity is a key factor indicating mitochondrial dysfunction. Abnormal changes in mitochondrial viscosity are closely related to various diseases and dysfunctions. Developing a mitochondrial viscosity response probe can provide new insights into these diseases. This study introduces a novel near-infrared fluorescent probe for the detection of mitochondrial viscosity in live cells.