Endoplasmic Reticulum Targeting Reactive Oxygen Species Sensor Based on Dihydrofluorescein: Application of Endoplasmic Reticulum Stress

Endoplasmic reticulum (ER) has a unique redox environment, which plays critical roles in the organelle's function and in its pathological responses such as ER stress. In this work, we introduce an ER-targeting fluorogenic reactive oxygen species (ROS) chemosensor (ER-Flu) from copper(I)-catalyzed alkyne-azide cycloaddition of 3-propargyl ester of 2′,7′-dichlorodihydrofluorescein diacetate and N₃-glibenclamide, which were adopted as a fluorogenic ROS sensing module and an ER-targeting module, respectively. Thereby, a series of confocal microscopic experiments of ER-Flu demonstrated that the sensor localizes in ER of the live cells and that ROS are elevated in the cells by ER stress inducers such as thapsigargin, brefeldin A, and tunicamycin.