RA is a chronic disorder associated with synovial inflammation that leads to the destruction of cartilage and subchondral bone. It has a 1 % incidence in the general population and causes significant pain, morbidity and mortality. Currently there is no cure for RA but novel immunomodulatory drugs have drastically changed disease outcome. Established diagnostic methods such as magnetic resonance imaging (MRI) do not facilitate definitive diagnosis or a clear estimation of the prognosis. To address this, scientists on the EU-funded NANODIARA (Development of novel nanotechnology based diagnostic systems for rheumatoid arthritis and osteoarthritis) project set out to develop superparamagnetic iron oxide nanoparticles (SPION) as a diagnostic tool. Researchers used polyvinyl alcohol (PVA) as the principal surface component and scaled up SPION production through a semi-automated synthesis and functionalisation process. For diagnostic applications in the human body, SPION were attached to biomarker-specific antibodies compatible with biomarker capturing in biofluids. To identify and measure early events in arthritis tissue destruction, the consortium used SPION with antibodies raised against specific pathologically cleaved tissue molecules. The in vivo application aimed at detecting early inflammation and articular cartilage destruction in joints of RA and OA patients. Toxicity studies in rats showed promising results and biodistribution analysis demonstrated specific localisation at the inflamed synovial membrane of arthritic knees. SPION was further utilised to enhance MRI imaging and was successfully implemented for the monitoring of dexamethasone treatment. This imaging method proved sensitive enough to detect small changes in the inflammatory response following treatment in the preclinical arthritis model. Overall, SPION-based in vivo imaging demonstrated the potential to detect disease-related molecular changes prior to existing imaging modalities. Implementation of this tool towards the diagnosis of RA should facilitate prompt treatment initiation and improve patient outcome.
Nanotechnology, antibodies, rheumatoid arthritis, inflammation, superparamagnetic iron oxide nanoparticles, MRI