A high lipid-soluble probe for ONOO− recognition in the endoplasmic reticulum and imaging of cerebral ischemia-reperfusion injury

IF 2.7 3区 化学 Q1 CHEMISTRY, ORGANIC
Yu-An Feng , Zi-Hao Liu , Wei Du , Ya-Wen Wang , Yu Peng
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引用次数: 0

Abstract

Cerebral ischemia/reperfusion injury (CIRI) is a highly damaging pathological process in stroke. In CIRI, ER stress is the main source of cellular reactive oxygen species (ROS) and significantly contributes to neurological damage. Among ROS, peroxynitrite (ONOO) exhibits potent oxidative and nucleophilic properties. Monitoring ONOO within the ER is essential for understanding and treating CIRI. However, the lack of probes capable of crossing the blood–brain barrier (BBB) and selectively targeting the ER has hindered progress in this field. To address this challenge, we developed a near-infrared fluorescent probe, , which was designed for both BBB penetration and ER-specific localization. This probe demonstrated high reactivity and superior lipid solubility. The in vitro BBB model assays confirmed its efficient BBB permeability, while imaging studies revealed its ability to dynamically monitor ER-associated ONOO under various conditions.

Abstract Image

内质网ONOO识别的高脂溶性探针及脑缺血再灌注损伤的影像学研究。
脑缺血再灌注损伤(CIRI)是脑卒中中一种高度损伤性的病理过程。在CIRI中,内质网应激是细胞活性氧(ROS)的主要来源,并显著促进神经损伤。在活性氧中,过氧亚硝酸盐(ONOO-)表现出强大的氧化和亲核性质。在急诊室内监测ONOO-对于理解和治疗CIRI至关重要。然而,缺乏能够穿过血脑屏障(BBB)并选择性靶向内质网的探针阻碍了这一领域的进展。为了解决这一挑战,我们开发了一种近红外荧光探针SWJT-27,它既能穿透血脑屏障,又能定位er特异性。该探针具有较高的反应活性和较好的脂溶性。体外血脑屏障模型分析证实了其有效的血脑屏障通透性,而影像学研究显示其在各种条件下动态监测er相关ONOO-的能力。
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来源期刊
Organic & Biomolecular Chemistry
Organic & Biomolecular Chemistry 化学-有机化学
CiteScore
5.50
自引率
9.40%
发文量
1056
审稿时长
1.3 months
期刊介绍: Organic & Biomolecular Chemistry is an international journal using integrated research in chemistry-organic chemistry. Founded in 2003 by the Royal Society of Chemistry, the journal is published in Semimonthly issues and has been indexed by SCIE, a leading international database. The journal focuses on the key research and cutting-edge progress in the field of chemistry-organic chemistry, publishes and reports the research results in this field in a timely manner, and is committed to becoming a window and platform for rapid academic exchanges among peers in this field. The journal's impact factor in 2023 is 2.9, and its CiteScore is 5.5.
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