Engineering an Activatable Near-Infrared Fluorogenic Probe for Hypochlorous Acid in Keloid Diagnosis and Therapeutic Evaluation

Keloid is a skin fibrosis disease characterized by continuous deposition of extracellular matrix and invasive expansion of the lesion. Hypochlorous acid (HOCl), an important member of the reactive oxygen family, has been proven to participate in the activation process of fibroblasts in various fibrosis diseases. However, the dynamic changes in keloid have not been fully explored. Herein, we constructed an activatable near-infrared fluorogenic (NIRF) probe DQFCl-HOCl for visualizing HOCl and exploring its association with the pathological activity of keloid. DQFCl-HOCl featured NIRF emission, rapid response, nanomolar-level detection sensitivity, and excellent selectivity. In cell models, DQFCl-HOCl could image exogenous and endogenous HOCl. More importantly, the HOCl fluorescence signal in keloid fibroblasts was markedly higher than that in normal dermal fibroblasts, and it decreased after intervention with RepSox or triamcinolone acetonide (TA). In a patient-derived xenograft model, DQFCl-HOCl could distinguish keloid tissue in mice and dynamically visualize the therapeutic effect of TA. Additionally, transcriptomic coexpression network analysis combined with Western blot results indicated that redox regulation pathways were closely coupled with the fibrotic signaling network centered on TGF-β. This work provided a new chemical imaging tool for tracing the redox microenvironment of keloid and evaluating therapeutic response.