Construction of a Golgi apparatus-localization polarity-responsive fluorescent probe with large Stokes shift to screen the small-molecule drugs for the inhibition of ferroptosis.

Abstract

Ferroptosis is a distinctive cell death form and has close connections with many diseases, and screening of ferroptosis-associated drug has great importance to delve into creative approaches against the currently intractable diseases. Herein, we developed a method for the ferroptosis-related small-molecule drugs screening by a GA-targeting polarity-responsive fluorescent probe (GP-1). The probe GP-1 showed large Stokes shifts in solvents (up to 194 nm), and displayed desirable sensitivity and selectivity to polarity. GP-1 was primarily distributed in Golgi apparatus (GA) rather than the other common organelles such as lysosome, mitochondria and endoplasmic reticulum (ER). Fluorescence imaging experiments revealed that erastin-induced ferroptosis could raise GA polarity noticeably. By using GA polarity as an indicator to assess the bioactivity of various small-molecule drugs, the imaging data showed that the natural active molecules (e.g. baicalein, rutin, curcumin, DHLA, lipoic acid, retinol, VE, 7-DHC) and edaravone can inhibit the significant changes of GA polarity, while the common Fe(II)-complexing agents (citric acid, tartaric acid) displayed nearly no inhibition effects to ferroptosis.