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 blood of rheumatoid arthritis (RA) 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 labelled EVs, derived from 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 RA patients show an overexpression of αV integrin and are effectively taken up by LPS/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 glucose transporter 1 (mGLUT1), 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 RA treatment.