The potential of autologous patient-derived circulating extracellular vesicles to improve drug delivery in rheumatoid arthritis

Abstract Recognizing the need for innovative therapeutic approaches in the management of autoimmune diseases, our current investigation explores the potential of autologous extracellular vesicles (EVs), derived from the blood of rheumatoid arthritis patients, to serve as therapeutic vectors to improve drug delivery. We found that circulating EVs derived from arthritic mice (collagen-induced arthritis model) express the joint/synovia homing receptor, αVβ3 integrin. Importantly, both autologous labeled EVs, derived from the blood of arthritic mice (collagen antibody-induced arthritis model) and healthy mice-derived EVs, exhibit targeted migration toward inflamed synovia without infiltrating healthy joints, as demonstrated by an in vivo imaging system. Furthermore, EVs derived from plasma of rheumatoid arthritis patients show an overexpression of αV integrin and are effectively taken up by lipopolysaccharides/tumor necrosis factor alpha (TNFα)-induced activated human synovial cell line in vitro, although interestingly the uptake of healthy EVs was found to be significantly increased. Notably, arthritic mice-derived circulating EVs, strongly express murine glucose transporter 1, which in turn can facilitate their binding to glucose-coated gold nanoparticles (previously shown to be conjugated with drugs for improved drug delivery). The significance of our results, lies in the identification of autologous tissue homing EVs as promising vectors, offering a novel avenue to enhance targeted delivery of anti-inflammatory/rheumatic drugs in rheumatoid arthritis treatment.