Lipid droplet-targeted and ratiometric fluorescent probe for imaging ClO in Rheumatoid arthritis model.

Abstract

BACKGROUND: Rheumatoid arthritis (RA) is a long-term, systemic autoimmune disease that primarily affects the synovial joints, causing chronic inflammation and eventual joint destruction. The underlying cause of RA is strongly associated with the excessive production of hypochlorite (ClO). Increased levels of ClOcan lead to oxidative damage in cells, playing a crucial role in the development and progression of the disease. Despite advances in research, detecting RA at its early stages remains difficult, especially since existing ratiometric fluorescent probes face significant challenges in accurately identifying changes in ClOlevels. RESULTS: To address this challenge, a new fluorescence probe, PT, was designed and synthesized for the detection and imaging of ClO. The design of PT incorporates an electron-rich phenothiazine core, which acts as both the recognition site and electron donor for ClO, while the benzothiazole unit serves as the electron acceptor. This creates a donor-π-acceptor structure that produces a clear ratiometric fluorescence signal at 490/664 nm. Notably, PT exhibits aggregation-induced emission (AIE) properties, demonstrating strong affinity for the co-localization imaging of lipid droplets, allowing for effective visualization of ClOin lipid droplets in living organisms. Moreover, PT was successfully used to detect elevated ClOlevels in a collagen-induced arthritis (CIA) mouse model, indicating that ClOcould serve as a potential biomarker for the diagnosis of RA. SIGNIFICANCE: The fluorescent probe PT offers a highly effective and reliable tool for imaging of the Rheumatoid arthritis with its excellent ratiometric fluorescence response and AIE properties. The unique ratiometric nature of PT allows for precise detection of ClOlevels in the RA mice model, while AIE characteristics of PT enable clear imaging and visualization of key pathological features in vivo.