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一种用于关节炎中铁死亡相关多硫化氢成像的近红外比率荧光探针。

A near-infrared ratiometric fluorescent probe for ferroptosis related hydrogen polysulfides imaging in arthritis.

作者信息

Cao Ting, Gong Yajie, Dong Wenhua, Li Mengjin, Gong Deyan, Fan Zhefeng

机构信息

Key Laboratory of Magnetic Molecules & Magnetic Information Materials Ministry of Education, The School of Chemical and Material Science, Shanxi Normal University, Taiyuan, 030031, PR China.

Honghu Hospital of Traditional Chinese Medicine, Jingzhou, 433200, PR China.

出版信息

Talanta. 2026 Jan 1;296:128475. doi: 10.1016/j.talanta.2025.128475. Epub 2025 Jun 17.

DOI:10.1016/j.talanta.2025.128475
PMID:40554064
Abstract

Hydrogen polysulfide (HS, n > 1) is considered a highly promising new signaling molecule that plays an irreplaceable key role in physiological regulation. Ferroptosis is primarily driven by iron-dependent accumulation of lipid peroxides related to reactive oxygen species under the action of iron. During the process of ferroptosis, large amounts of ROS are produced, which promote an increase in intracellular levels of hydrogen polysulfide. There are studies indicating a close and undeniable association between ferroptosis and arthritis. Based on this, our study synthesized a near-infrared ratiometric fluorescent probe TMN-S for in vivo and in vitro detection and imaging of HS. TMN-S exhibits high sensitivity (DL = 0.38 μM) and selectivity towards HS, and cytotoxicity assays have shown that it has low biological toxicity and good biocompatibility. The nucleophilic substitution mechanism between the probe and HS was verified through spectroscopic experiments and NMR analysis, and the probe TMN-S has been effectively used for track and image endogenous and exogenous HS sources in cells. In addition, the probe monitored the changes in intracellular HS expression levels during ferroptosis in a ratio signal mode. More importantly, TMN-S successfully achieved imaging of HS in arthritis mice associated with ferroptosis. This provides an effective experimental tool for a deeper understanding of the mechanism of action of HS in arthritis caused by ferroptosis.

摘要

多硫化氢(HS,n>1)被认为是一种极具前景的新型信号分子,在生理调节中发挥着不可替代的关键作用。铁死亡主要由铁依赖性脂质过氧化物的积累驱动,这些脂质过氧化物在铁的作用下与活性氧有关。在铁死亡过程中,会产生大量活性氧,从而促进细胞内多硫化氢水平的升高。有研究表明铁死亡与关节炎之间存在密切且不可否认的关联。基于此,我们的研究合成了一种近红外比率荧光探针TMN-S,用于体内外多硫化氢的检测和成像。TMN-S对多硫化氢表现出高灵敏度(检测限=0.38μM)和选择性,细胞毒性试验表明它具有低生物毒性和良好的生物相容性。通过光谱实验和核磁共振分析验证了探针与多硫化氢之间的亲核取代机制,并且探针TMN-S已有效地用于追踪和成像细胞内源性和外源性多硫化氢来源。此外,该探针以比率信号模式监测了铁死亡过程中细胞内多硫化氢表达水平的变化。更重要的是,TMN-S成功实现了在与铁死亡相关的关节炎小鼠体内多硫化氢的成像。这为更深入了解多硫化氢在铁死亡引起的关节炎中的作用机制提供了一种有效的实验工具。

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