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

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.