Ultra-large stokes-shifted NIR fluorescent probes for the diagnosis and treatment of rheumatoid arthritis via metal-free tracking of carbon monoxide

Abstract

Early diagnosis of rheumatoid arthritis (RA) is essential for preventing disease progression and improving prognosis. This study proposes the use of carbon monoxide (CO) as a potential biomarker for RA. Two fluorophores, HM-OH and DHM-OH, were designed and synthesized, using DHM-OH due to its superior spectroscopic properties. The combination of DHM-OH with allyl bromide produced the fluorescent probe DHM-CO, which had a large Stokes shift (302 nm) and a long emission wavelength (882 nm). DHM-CO enabled metal-free catalytic detection of CO. The probe was demonstrated to have excellent water solubility, photostability, and high sensitivity to CO; therefore, it could selectively respond to CO without interference from other substances. The limit of detection of the probe in the detection of CORM-3, a CO precursor, was as low as 0.027 μM. DHM-CO was successfully used for the imaging of endogenous and exogenous CO in A549 cells. It was also successful in the tracking of CO in RA models, revealing that the CO concentrations in RA joints were significantly higher compared to that in normal joints. Additionally, the therapeutic effect of methotrexate (MTX) on RA was verified. This study introduces the first imaging of CO in RA, offering a valuable tool for early diagnosis and treatment of RA.