Two-photon imaging for visualizing polarity in lipid droplets during chemotherapy induced Ferroptosis

As a novel pattern of regulated cell death (RCD), Ferroptosis is induced by lipid peroxide-dependent iron accumulation, which is associated with reactive oxygen species (ROS). Ferroptosis regulates cell death via ROS accumulation-related lipid peroxides accumulation, affecting the structure and polarity of lipid droplets (LDs). Compared with reactive fluorescent probes, environment-sensitive fluorescent probes allow for maximum preservation of the intracellular environment while monitoring metabolic activity in situ, resulting in more accurate monitoring results. In this study, a polarity-sensitive two-photon fluorescent probe with anchoring capacity in LDs, LIP-Pola, is reported and applied to monitor the polarity of LDs during cell Ferroptosis by in situ imaging analysis of cell Ferroptosis via LDs polarity changes. Additionally, Paclitaxel is shown to increase the Ferroptosis level from data of cells and tumor tissue sections, suggesting that Paclitaxel may deactivate tumor cells by regulating Ferroptosis.