Utilizing a Solvatochromic Optical Agent to Monitor the Polarity Changes in Dynamic Liver Injury Progression

Abstract

Unraveling the changing rule of endoplasmic reticulum (ER) polarity is of significance for liver injury. However, the rule of the ER polarity changes during the occurrence and progression of liver injury remains a mystery. Toward that, a unique fluorescent probe, ERNT, capable of imaging ER polarity in multiple liver injury models with high accuracy and fidelity was designed herein. In light of its excellent solvatochromism, the ER polarity was determined to be higher in the case of endoplasmic reticulum stress (ERS) induced by tunicamycin and dithiothreitol than that of the normal state at the cell level. Importantly, with the assistance of the PerkinElmer IVIS Spectrum imaging system and the powerful tool of ERNT, our work first revealed that the ER polarity increases with the evolution of liver injuries. Moreover, as a demonstration, ERNT achieved evaluating hepatoprotective drug efficacy by detecting ER polarity, confirming its high clinical application prospect. Thus, our work not only first unravels the rule of ER polarity in dynamic liver injury progression but may also inspire more diagnostic and therapeutic programs for liver diseases shortly.

Lipid Droplet-Specific Dual-Response Fluorescent Probe for the Detection of Polarity and H2O2 and Its Application in Living Cells

“…Borate is proved to be an excellent recognition site for H 2 O 2 , which can not only effectively quench the fluorescence of naphthalimide but also exhibit the advantages of rapidity, sensitivity, and high selectivity to H 2 O 2 . As for polarity detection, probes are usually constructed by D−π–A type organic fluorescent dyes with the ICT effect, − which display low fluorescence intensity in strong polar medium, but weakly polar regions within cells can be imaged (membranes and lipid droplets), so compound 1 is chosen to image polarity to avoid spectral overlap with naphthalimide. Therefore, NATPA is designed and synthesized by the route shown in Scheme S1, and its structure is characterized by 1 H NMR, 13 C NMR, and HRMS (ESI).…”

Recent progress in small-molecule fluorescent probes for endoplasmic reticulum imaging in biological systems

“…20), to monitor the ER polarity changes during liver injury. 115 For the first time, it was revealed that the polarity gradually increased with an increase in the severity of liver damage. Furthermore, the protective effect of the hepatoprotective drug was evaluated clearly by visualization of the polarity changes.…”

Molecular Fluorescent Probes for Liver Tumor Imaging

“…In 2021, Lin et al . developed a fluorescent probe ERNT for endoplasmic reticulum (ER) polarity monitor (Figure 11A) [51] . This probe can detect the polarity change in the liver damage process including fatty liver, liver fibrosis, liver cirrhosis, and liver cancer in the absence (Figure 11B) and presence of drug stimulation (Figure 11C), which are benefitable for the study in the liver tumor and environmental polarity.…”