Molecular engineering for construction of a novel ONOO−- activated multicolor fluorescent nanoprobe for early diagnosis and assessing treatment of arthritis in vivo

Abstract

Early diagnosis and assessment of the therapeutic effect of arthritis requires a reliable bioanalytical method to quantitatively and selectively detect the biomarkers peroxynitrite (ONOO−) in inflammatory diseases. Compared with previously reported probes for the specific detection of ONOO−, molecular engineering based on ONOO−-activated multicolor fluorescence nanoprobes will have the advantages of providing multi-channel information and be more suitable for bioimaging in multicomponent complex environments. Herein, for the first time, a fluorescent nanoprobe (CSU-FT) based on fluorescence resonance energy transfer (FRET), which can be activated by ONOO−, was constructed for multicolor fluorescence imaging, diagnosis and treatment of arthritis in inflammatory mice. Specifically, an energy transfer scaffold was constructed by conjugation of a near-infrared (NIR) xanthane fluorophore with a rhodamine B fluorophore and multicolor by ONOO−-modulated, which was then grafted onto sodium chondroitin sulfate (CSNa) to form CSU-FT through self-assembly. This nanoprobe shows a fast response time (<20s), outstanding selectivity and excellent detection limits as low as 11.7 nM. Interestingly, CSU-FT has been successfully used for intracellular multichannel imaging of endogenous ONOO− production as well as for diagnosis and treatment in a mice model of arthritis with impressive results, revealing practical application in physiological and pathological connection between ONOO− and arthritis.