Direct Intramolecular Chemiexcitation Strategy Enables Sensitive Chemiluminescence Imaging of HOCl in Rheumatoid Arthritis

作者：Han Chen, Zhihui Jia, Tengfei Zhang, Chiyuan Wei, Rong Wang, Hong‐Min Meng, Zhaohui Li · 发表于：ACS Sensors · 年份：2025 · DOI：10.1021/acssensors.5c02228 · 被引用次数：5 · 研究领域：Neutrophil, Myeloperoxidase and Oxidative Mechanisms、Rheumatoid Arthritis Research and Therapies、Adenosine and Purinergic Signaling

As a pivotal pathophysiological biomarker, hypochlorous acid (HOCl) necessitates sensitive detection technologies to resolve its spatiotemporal dynamics in biological systems. Excitation-free chemiluminescent probes circumvent tissue autofluorescence interference intrinsic to fluorescence imaging, thereby enabling high-contrast deep-tissue monitoring. However, current chemiluminescent probes often demand intricate modifications for HOCl recognition, resulting in compromised stability and sensitivity. Herein, employing intramolecular energy transfer, we engineered a HOCl-directly activated chemiluminescent probe for real-time visualization of oxidative stress in pathologically relevant models. This design leverages the carbon–carbon double bond as an intrinsic activation site, which enables efficient HOCl detection with rapid response while avoiding intermolecular energy dissipation. Crucially, electron-withdrawing group modification further enhanced sensitivity (LOD: 20 nM vs 179 nM), positioning CL-2 competitively among state-of-the-art HOCl probes and offering a novel approach for future probe performance optimization. Mechanistic studies revealed that HOCl oxidizes the ethylene bridge to peroxide intermediates; their exothermic decomposition directly excites the intramolecular fluorophore. To validate its bioimaging potential, we validated CL-2 ’s in vivo responsiveness and applied it to a rheumatoid arthritis mouse model. The results demonstrated that CL-2 selectively ill...