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一种可激活的荧光探针可用于体内评估类风湿关节炎中的过氧亚硝酸盐水平。

An activatable fluorescent probe enables in vivo evaluation of peroxynitrite levels in rheumatoid arthritis.

机构信息

Collaborative Innovation Center for Advanced Organic Chemical Materials Co-constructed by the Province and Ministry, Ministry of Education Key Laboratory for the Synthesis and Application of Organic Functional Molecules, College of Chemistry and Chemical Engineering, Hubei University, Wuhan, 430062, China; Wuhan Business University, Wuhan, 430100, China.

Collaborative Innovation Center for Advanced Organic Chemical Materials Co-constructed by the Province and Ministry, Ministry of Education Key Laboratory for the Synthesis and Application of Organic Functional Molecules, College of Chemistry and Chemical Engineering, Hubei University, Wuhan, 430062, China.

出版信息

Talanta. 2023 Jan 15;252:123811. doi: 10.1016/j.talanta.2022.123811. Epub 2022 Aug 6.

DOI:10.1016/j.talanta.2022.123811
PMID:35987124
Abstract

An activatable probe able to detect RONS level underlying the development of rheumatoid arthritis (RA) would be far-reaching for the diagnosis and drug efficacy assessment of RA. Despite more and more evidence suggests that ONOO is an important signaling molecule participating in the RA disease, only rare fluorescent probes can detect ONOO in this disease with satisfying performance. To this end, we designed and synthesized a novel activatable AIE fluorescent probe (DPPO-PN) for the detection of ONOO levels in RA. The probe linearly responds to 0-10 μM ONOO with a significant far-red fluorescence enhancement at 632 nm in 30 s (F/F = 161-fold, LOD = 10 nM) upon the excitation of 490 nm, elucidating excellent sensing abilities for ONOO in cuvettes. Moreover, the fluctuations of intracellular ONOO levels caused by adscititious adding or stimulant provoking could be real-time captured and visualized with this probe by confocal imaging. Further, the intravital imaging of ONOO in LPS-induced and CFA-induced RA mouse models also can be achieved with the aid of the probe, substantiating the burst of ONOO in the RA process. Therefore, this work not only offers an auxiliary tool for the diagnosis of RA but also would benefit our understanding of the ONOO's roles in RA.

摘要

一种能够检测类风湿关节炎 (RA) 发病机制下 RONS 水平的可激活探针,对于 RA 的诊断和药物疗效评估将具有深远意义。尽管越来越多的证据表明,ONOO 是一种参与 RA 疾病的重要信号分子,但只有极少数荧光探针能够以令人满意的性能检测到这种疾病中的 ONOO。为此,我们设计并合成了一种新型的可激活 AIE 荧光探针(DPPO-PN),用于检测 RA 中的 ONOO 水平。该探针在线性响应 0-10 μM ONOO 的同时,在 30 秒内以 490nm 激发时在 632nm 处产生显著的远红光荧光增强(F/F=161 倍,LOD=10nM),表明其在比色皿中对 ONOO 具有出色的传感能力。此外,通过共聚焦成像,该探针可以实时捕获和可视化由于外加添加或刺激物引发而导致的细胞内 ONOO 水平的波动。此外,借助该探针还可以对 LPS 诱导和 CFA 诱导的 RA 小鼠模型中的 ONOO 进行活体成像,证实了 ONOO 在 RA 过程中的爆发。因此,这项工作不仅为 RA 的诊断提供了辅助工具,还有助于我们理解 ONOO 在 RA 中的作用。

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Activatable fluorescent probes for imaging and diagnosis of rheumatoid arthritis.用于类风湿性关节炎成像和诊断的荧光探针
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