An endoplasmic reticulum-targeting fluorescent probe for the visualization of the viscosity fluctuations during...

Ferroptosis is an unique iron-dependent cell death form and currently has been shown to closely relate with ER. Revealing the viscosity fluctuations of ER during ferroptosis is of great significance not only to monitor the occurrence and development of iron poisoning, but also to deeply understand the biological effects of ER in ferroptosis. Herein, we present an ER-targeting fluorescent probe (PV1) to detect viscosity changes of ER during ferroptosis. PV1 utilized a rotatable C-C bond to connect the two rigid π-systems, and responded viscosity by the regulation of the coplanarity of these two planes. PV1 displayed desirable sensitivity and selectivity to viscosity. The biological imaging results suggested that PV1 mainly distributed at ER in live cells, and the viscosity of ER exhibited an evident increase in the process of erastin-induced ferroptosis. After the simultaneous incubation of cells with erastin and Fer-1 or VE, the viscosity of ER showed no marked change, and it suggested that the erastin-induced ferroptosis could be inhibited by Fer-1 and VE. We expect that the developed probe could provide a feasible and rapid method for the in-depth study of the ferroptosis-based disease treatment and drug design.