Multifunctional Nanoparticles Co-Loaded with Perfluoropropane, Indocyanine Green, and Methotrexate for Enhanced Multimodal Imaging of Collagen-Induced Arthritis

Rheumatoid arthritis (RA), a common chronic inflammatory joint disease with features of synovitis and pannus formation, may lead to irreparable joint damage and disability. Methotrexate (MTX) is known as the cornerstone of therapy for RA. However, the therapeutic effects of MTX are unsatisfactory due to its low retention in the inflammatory joints as well as systemic toxic effects. Fortunately, the use of multifunctional nanoparticles for diagnostics and in treatment shows potential for application as a strategy for traceable and targeted RA therapy. This research aims to develop novel nanoparticles that carry with perfluoropropane (PFP), indocyanine green (ICG), and MTX and investigate the corresponding enhancement in multimodal imaging both in vitro and in vivo. A modified double emulsion method was applied for the construction of encapsulated PFP-O2, ICG, and MTX (OIM@NPs), and the essential properties of the developed NPs were determined. The fluorescence and ultrasonic and photoacoustic imaging characteristics were experimentally evaluated both in in vitro and in vivo models. The OIM@NPs are stable and efficient nanoagents. They enable more targeted distribution in the inflammatory joints in RA rats. Moreover, the NPs play an important role as contrast agents for prominent ultrasound and photoacoustic imaging after laser and low-intensity focused ultrasound excitation, providing precision guidance and monitoring for subsequent treatment. This research may provide a novel and efficient strategy to better enable monitoring in inflammatory joints of RA patients and the developed NPs may be a promising nanoplatform for integrating multimodal image monitoring.