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构建用于类风湿关节炎中 HClO 生物成像的双“关-开”近红外荧光探针。

Construction of a dual "off-on" near-infrared fluorescent probe for bioimaging of HClO in rheumatoid arthritis.

机构信息

State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering and Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing, 210023, China.

State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering and Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing, 210023, China.

出版信息

Talanta. 2024 Dec 1;280:126721. doi: 10.1016/j.talanta.2024.126721. Epub 2024 Aug 23.

DOI:10.1016/j.talanta.2024.126721
PMID:39178513
Abstract

Hypochlorous acid (HClO) serves as a critical biomarker in inflammatory diseases such as rheumatoid arthritis (RA), and its real-time imaging is essential for understanding its biological functions. In this study, we designed and synthesized a novel probe, RHMB, which ingeniously integrates rhodamine B and methylene blue fluorophores with HClO-specific responsive moieties into a single molecular framework. Upon exposure to HClO, RHMB exhibited significant dual-channel fluorescence enhancement characterized by high sensitivity (LODs of 2.55 nM and 14.08 nM), excellent selectivity, and rapid response time (within 5 s). Notably, RHMB enabled reliable imaging of both exogenous and endogenous HClO in living cells and in zebrafish, employing a unique duplex-imaging turn-on approach that highlighted its adaptability across various biological contexts. Furthermore, RHMB effectively monitored HClO fluctuations in an RA mouse model and assessed the therapeutic efficacy of diclofenac (Dic) in alleviating RA symptoms. These findings underscore the potential of RHMB as an invaluable tool for elucidating the biological roles of HClO in various diseases.

摘要

次氯酸(HClO)可作为类风湿性关节炎(RA)等炎症性疾病的关键生物标志物,实时成像对于了解其生物学功能至关重要。在这项研究中,我们设计并合成了一种新型探针 RHMB,它巧妙地将罗丹明 B 和亚甲蓝荧光团与 HClO 特异性响应部分集成到单个分子框架中。暴露于 HClO 后,RHMB 表现出显著的双通道荧光增强,具有高灵敏度(LOD 分别为 2.55 nM 和 14.08 nM)、出色的选择性和快速的响应时间(<5 s)。值得注意的是,RHMB 能够在活细胞和斑马鱼中可靠地成像外源性和内源性 HClO,采用独特的双通路成像开启方法,突出了其在各种生物背景下的适应性。此外,RHMB 还能够有效监测 RA 小鼠模型中 HClO 的波动,并评估双氯芬酸(Dic)缓解 RA 症状的治疗效果。这些发现突显了 RHMB 作为阐明 HClO 在各种疾病中生物学作用的宝贵工具的潜力。

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