A D-π-A-π-D type structure-based fluorescent probe for revealing the fluctuations of the ER polarity during ferroptosis.

Ferroptosis is a novel Fe(II)-mediated oxidative cell death form, and is closely related with endoplasmic reticulum (ER). Exploring the fluctuation of ER polarity during ferroptosis is highly important for the in-depth study of the biological roles of ER in ferroptosis. Herein, we present a ratiometric probe (BNS) for revealing the changes of the ER polarity in the living cells experiencing ferroptosis. BNS employed a D-π-A-π-D type structure as the polarity-sensitive fluorophore, and selected p-toluenesulfonamide as the ER-targeting unit. Theoretical calculations suggested that the response mechanism of BNS to polarity was based on ICT, and two ICT processes appeared when BNS was at excited state. Cell imaging results demonstrated that BNS possessed desirable ER-targeting capability, and erastin-induced ferroptosis could increase the ER polarity of the living cells. Moreover, similarly to vitamin E (VE) and deferoxamine (DFO), dihydrolipoic acid (DHLA) could inhibit the changes of the ER polarity during erastin-induced ferroptosis. We expect that the probe could provide a convenient method to rapidly monitor ferroptosis and design novel drugs for the treatment of ferroptosis-relevant diseases.