Near-Infrared Fluorescent Lysosomal Viscosity Probe with Strong Solid Fluorescence for Rapid Imaging of Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) is a chronic disease of widespread concern worldwide, and there is an urgent need to develop sensitive methods for the rapid detection of RA. Previous studies have shown that RA is closely related to lysosomal dysfunction. Lysosomal viscosity is an important microenvironmental parameter reflecting the state of lysosomes, but due to the lack of probes to demonstrate the correlation between lysosomal viscosity and RA, the changes in lysosomal viscosity during RA remain unclear. For this purpose, we report herein a lysosome-targeted near-infrared fluorescent molecular rotor probe DSMP to investigate the correlation between lysosomal viscosity and RA. This probe utilizes dicyanomethylene-4H-benzothiopyran as an electron acceptor in the fluorophore and a piperazine unit as an electron donor and targeting group for lysosomes. In addition, DSMP shows strong solid fluorescence and a sensitive response to viscosity and can effectively target lysosomes to detect changes in lysosomal viscosity in live cells. Based on this, we established a mouse model of RA using λ-carrageenan. Mice imaging studies show that DSMP can quickly image RA, and RA tissues exhibit fluorescence signals significantly brighter than those of normal joint tissues. This indicates an increase in lysosomal viscosity during RA; therefore, lysosomal viscosity can serve as an indicator for rapid detection of RA, and DSMP can be an effective tool for RA imaging and research.