Rational design of a symmetric double rotor-based fluorescent probe for revealing LDs viscosity changes during ferroptosis

Abstract

Investigation of lipid droplets (LDs) viscosity is vital for revealing the function of LDs and the pathogenesis of related diseases. Thus, the development of fluorescent probes that can detect LDs viscosity variations is highly desired. Inspired by the traditional Chinese dragon boat, a symmetric double-rotor-based LDs-specific fluorescent probe PBBA was fabricated. The probe PBBA ((2E,2′E)-3,3'-(1,4-phenylene)bis(2-(benzo[d]thiazol-2-yl) acrylonitrile), C26H14N4S2) exhibited high selectivity and favorable sensitivity for viscosity changes with low interference from other factors. Cell imaging with PBBA at a concentration of only 2 μM presented obvious viscosity increases in LDs during erastin- or RSL3-induced ferroptosis, while nearly no change was observed when the inhibitor ferrostatin 1 (Fer-1) was added simultaneously. This study provides a new strategy for the design of viscosity-sensitive probes and contributes to a robust molecular tool to promote an in-depth understanding of the Fenton reaction and lipid peroxidation in LDs during ferroptosis.