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Rheumatoid arthritis (RA) is a common chronic autoimmune inflammatory disease, and its etiology is closely related to the overproduction of hypochlorous acid (HClO). However, early detection of RA using an activatable near-infrared-II (NIR-II, 1000–1700 nm) fluorescent probe remains challenging. Herein, we first report an “OFF–ON” NIR-II fluorescent probe named PTA (phenothiazine triphenylamine) for imaging HClO in deep-seated early RA. Electron-rich phenothiazine in the core of PTA was utilized as both an HClO-recognition moiety and a precursor of electron acceptors, displaying a typical donor–acceptor–donor structure with excellent NIR-II emission at 936/1237 nm once reacted with HClO. The probe PTA exhibited good water solubility, high photostability, and rapid response capability toward HClO within 30 s. Moreover, it was able to sensitively and specifically detect exogenous and endogenous HClO in living cells in both visible and NIR-II windows. Notably, PTA enabled the sensitive and rapid visualization of HClO generation in an inflammatory RA mouse model, showing a 4.3-fold higher NIR-II fluorescence intensity than that in normal hindlimb joints. These results demonstrate that PTA holds great promise as a robust platform for diagnosis of HOCl-mediated inflammatory disorders.
中文翻译：
类风湿关节炎（RA）是一种常见的慢性自身免疫性炎症性疾病，其病因与次氯酸（HClO）的过量产生密切相关。然而，使用可激活的近红外-II（NIR-II，1000-1700 nm）荧光探针早期检测 RA 仍然具有挑战性。在此，我们首先报告了一种名为PTA（吩噻嗪三苯胺）的“OFF-ON”NIR-II 荧光探针，用于对深部早期 RA 中的 HClO 进行成像。PTA核心中的富电子吩噻嗪被用作 HClO 识别部分和电子受体的前体，显示出典型的供体-受体-供体结构，一旦与 HClO 反应，在 936/1237 nm 处具有出色的 NIR-II 发射。探针PTA表现出良好的水溶性、高光稳定性和 30 秒内对 HClO 的快速响应能力。此外，它能够在可见光和 NIR-II 窗口中灵敏且特异性地检测活细胞中的外源性和内源性 HClO。值得注意的是，PTA使炎性 RA 小鼠模型中 HClO 生成的敏感和快速可视化成为可能，显示出比正常后肢关节高 4.3 倍的 NIR-II 荧光强度。这些结果表明，PTA有望成为诊断 HOCl 介导的炎症性疾病的强大平台。 |
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