A near-infrared fluorescent probe with rapid-response hypochlorite for imaging rheumatoid arthritis and wound healing in vivo.

Real-time monitoring of hypochlorite (ClO-) fluctuations in inflamed tissues is crucial for evaluating the onset, progression, and prognosis of inflammatory diseases such as rheumatoid arthritis (RA). In this study, we rationally developed a small-molecule fluorescent probe (SX-ClO) based on a malononitrile-isophorone fluorophore skeleton coupled with a diaminomaleonitrile moiety as the ClO--responsive unit. The probe operated through an intramolecular ICT modulation mechanism upon specific reaction with ClO-, enabling a remarkable fluorescence turn-on response with high selectivity, excellent sensitivity, and minimal background interference. SX-ClO demonstrated a reliable ability to visualize both endogenous and exogenous ClO- in live RAW 264.7 macrophages, thereby facilitating dynamic evaluation of intracellular oxidative microenvironments. Beyond in vitro performance, SX-ClO achieved high-contrast fluorescence imaging of ClO- accumulation in λ-carrageenan-induced RA mouse joints, effectively distinguishing inflamed joints from healthy ones. Moreover, the probe successfully detected elevated ClO- levels in MRSA-infected wound tissues, providing clear visualization of bacterial infection-associated oxidative bursts. Overall, these properties enable real-time visualization and dynamic monitoring of pathological processes at the molecular level, highlighting its potential for clinical translation in early diagnosis and disease progression tracking.