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用于监测非酒精性脂肪性肝病中过氧亚硝酸盐的高灵敏近红外荧光探针:实现早期诊断和治疗评估。

Highly sensitive near-infrared fluorescent probe for monitoring peroxynitrite in nonalcoholic fatty liver disease: Toward early diagnosis and therapeutic evaluation.

机构信息

School of Materials and Chemical Engineering, Ningbo University of Technology, Ningbo, 315211, PR China; Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, 410081, PR China.

Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, 410081, PR China.

出版信息

Talanta. 2025 Jan 1;281:126865. doi: 10.1016/j.talanta.2024.126865. Epub 2024 Sep 11.

DOI:10.1016/j.talanta.2024.126865
PMID:39265422
Abstract

Nonalcoholic fatty liver disease (NAFLD) poses a significant global health concern, necessitating precise diagnostic tools and effective treatment strategies. Peroxynitrite (ONOO), a reactive oxygen species, plays a pivotal role in NAFLD pathogenesis, highlighting its potential as a biomarker for disease diagnosis and therapeutic evaluation. This study reports on the development of a near-infrared (NIR) fluorescent probe, designated DRP-O, for the selective detection of ONOO with high sensitivity and photostability. DRP-O exhibits rapid response kinetics (within 2 min) and an impressive detection limit of 2.3 nM, enabling real-time monitoring of ONOO dynamics in living cells. Notably, DRP-O demonstrates excellent photostability under continuous laser irradiation, ensuring reliable long-term monitoring in complex biological systems. We apply DRP-O to visualize endogenous ONOO in living cells, demonstrating its potential for diagnosing and monitoring NAFLD-related oxidative stress. Furthermore, DRP-O effectively evaluates the efficacy of therapeutic drugs in NAFLD cell models, underscoring its potential utility in drug screening studies. Moreover, we confirm DRP-O to enable selective identification of fatty liver tissues in a mouse model of NAFLD, indicating its potential for the early diagnosis of NAFLD. Collectively, DRP-O represents a valuable tool for studying ONOO dynamics, evaluating drug efficacy, and diagnosing NAFLD, offering insights into novel therapeutic strategies for this prevalent liver disorder.

摘要

非酒精性脂肪性肝病 (NAFLD) 是一个全球性的健康问题,需要精确的诊断工具和有效的治疗策略。过氧亚硝酸盐 (ONOO-) 作为一种活性氧物质,在 NAFLD 的发病机制中起着关键作用,这突出了它作为疾病诊断和治疗评估的生物标志物的潜力。本研究报告了一种近红外 (NIR) 荧光探针 DRP-O 的开发,用于选择性检测 ONOO-,具有高灵敏度和光稳定性。DRP-O 表现出快速的响应动力学(在 2 分钟内)和令人印象深刻的检测限为 2.3 nM,能够实时监测活细胞中 ONOO-的动态。值得注意的是,DRP-O 在连续激光照射下表现出优异的光稳定性,确保在复杂的生物系统中进行可靠的长期监测。我们应用 DRP-O 来可视化活细胞内的内源性 ONOO-,证明了其在诊断和监测与 NAFLD 相关的氧化应激方面的潜力。此外,DRP-O 有效地评估了 NAFLD 细胞模型中治疗药物的疗效,突出了其在药物筛选研究中的潜在应用。此外,我们证实 DRP-O 能够选择性地识别 NAFLD 小鼠模型中的脂肪肝组织,表明其具有用于 NAFLD 的早期诊断的潜力。总之,DRP-O 是研究 ONOO-动力学、评估药物疗效和诊断 NAFLD 的有价值的工具,为这种常见的肝脏疾病提供了新的治疗策略的见解。

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