A near-infrared endoplasmic reticulum-targeted fluorescent probe to visualize the fluctuation of SO2 during endoplasmic reticulum stress

Abstract

• The first near-infrared fluorescent probe ( MSO-SO 2 ) targeted to the endoplasmic reticulum for the detection of SO 2. • Using dimalononitrile isophorone based fluorescent platforms that have large Stokes shift (∼135 nm). • The robust probe with rapidly and highly selective “protect-deprotect” response to SO 2 . • Realizing the imaging of SO 2 in the living cells, zebrafish, and mice. • Visualized the fluctuations of SO 2 during the endoplasmic reticulum stress, for the first time. Sulfur dioxide (SO 2 ), as a significant gas signal substance, plays an imperative physiological function in life systems and participates in a variety of metabolic pathways. Relevant research has found that SO 2 , as a reducing agent, may play an important role in protecting cells from endoplasmic reticulum (ER) stress. Therefore, studying the changes of SO 2 in cells under ER stress is extremely valuable. But so far, developing an effective near-infrared (NIR) fluorescent probe to detect SO 2 in the ER stress remains a major challenge. In this paper, the first near-infrared (NIR) fluorescent probe ( MSO-SO 2 ) targeted to the ER was constructed to recognize SO 2 . The probe MSO-SO 2 with dicyanoisophorone derivative as the fluorescent parent is based on the deprotection reaction site mediated by SO 2 as the response group (levulinic acid), which was applied for highly selective and sensitive detection for SO 2 . Furthermore, the biological trials have found that the unique probe targets ER well and has been effectively implemented in the living systems for SO 2 imagery. Most importantly, the production and consumption of SO 2 were discovered, for the first time, in dithiothreitol-induced ER stress by using the novel probe, which is beneficial for revealing the role of SO 2 in ER-associated diseases.