1. Endoplasmic reticulum-targeted fluorescent probe with aggregation-induced emission features for imaging peroxynitrite in drug-induced liver injury model.
- Author
-
Zhang H, Yang Y, Xie F, Lan Y, Li L, Song Z, Gao L, Huang Y, and Xiao P
- Subjects
- Humans, Animals, Mice, Hep G2 Cells, Biosensing Techniques methods, Endoplasmic Reticulum Stress drug effects, Molecular Docking Simulation, Optical Imaging methods, Peroxynitrous Acid metabolism, Peroxynitrous Acid chemistry, Chemical and Drug Induced Liver Injury pathology, Chemical and Drug Induced Liver Injury metabolism, Fluorescent Dyes chemistry, Endoplasmic Reticulum metabolism, Acetaminophen toxicity, Acetaminophen adverse effects
- Abstract
Drug-induced liver injury (DILI) poses a severe threat to public health. Endoplasmic reticulum (ER) stress contributes significantly to DILI pathogenesis, with peroxynitrite (ONOO
- ) identified as a pivotal indicator. However, the temporal and spatial fluctuations of ONOO- associated with ER stress in the pathogenesis of DILI remain unclear. Herein, a novel ER-specific near-infrared (NIR) probe (QM-ONOO) with aggregation-induced emission (AIE) features for monitoring ONOO- fluctuations in DILI was elaborately constructed. QM-ONOO exhibited excellent ER-targeting specificity, a large Stoke's shift, and a low detection limit (26.9 nM) toward ONOO- . QM-ONOO performed well in imaging both exogenous and endogenous ONOO- in HepG2 cells. Furthermore, molecular docking calculations validated the ER-targeting mechanism of QM-ONOO. Most importantly, using this probe allowed us to intuitively observe the dynamic fluctuations of ONOO- during the formation and remediation processes of DILI in the acetaminophen (APAP)-induced mouse model. Consequently, this work provides a promising tool for in-depth research of ONOO- associated pathological processes in DILI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)- Published
- 2024
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