Revealing the Viscosity Changes in Lipid Droplets during Ferroptosis by the Real-Time and In Situ Near-Infrared Imaging.

Ferroptosis is characterized by the massive lipid peroxidation, and recently has been demonstrated to be closely associated with lipid droplets (LDs). However, the changes of LDs viscosity during ferroptosis are still unrevealed. Herein, we present the changes of the LDs viscosity during ferroptosis by a novel viscosity-sensitive near-infrared (NIR) fluorescent probe (BDHT). Probe BDHT (2-(benzo[d]thiazol-2-yl)-7-(4-(dimethylamino)phenyl)hepta-2,4,6-trienenitrile, C22H19N3S) showed highly sensitive and selective response to viscosity, mainly distributed in cellular LDs. By means of the real-time and in situ NIR imaging, we discovered that the LDs viscosity showed an obvious increase in HeLa cells during the erastin-induced ferroptosis process, while it displayed nearly no change when the cells were simultaneously treated with ferrostatin-1, which is a common inhibitor of ferroptosis. It is also confirmed that the LDs viscosity increased in several types of the cancer cells of erastin-induced and RSL3-induced ferroptosis. We expect that this new NIR probe could provide an effective approach to rapidly monitor ferroptosis, and these findings could greatly promote the in-depth understanding of the biological effects of LDs during ferroptosis.