Ab0076 the Therapeutic Potential of Circulating Autologous Tissue Homing Extracellular Vesicles for the Management of Rheumatoid Arthritis Patients

Abstract

BackgroundProgress has been achieved with the introduction of biologics for the management of inflammatory/autoimmune diseases such as rheumatoid arthritis (RA), however such medications induce immune suppression, which is nonselective to the pathogenesis of the disease, resulting in higher rates of infections. Therefore, there are unmet medical needs in the treatment of such diseases, which should be addressed by novel approaches. Accumulating evidence suggests that extracellular vesicles (EVs) play a role in the establishment, maintenance and modulation of autoimmune processes.ObjectivesIn the current study, we hypothesized that isolation of circulating autologous tissue-specific homing EVs from RA patients - may improve the delivery of current FDA-approved anti-inflammatory drugs, which will be encapsulated into these EVs. The drug-loaded EVs will be injected back to the diseased subjects and will naturally find their way to the inflamed tissue.ResultsIndeed, we found that autologous labeled EVs, expressing joint/synovia-specific homing receptors (e.g. αVβ3 integrin), derived from blood of diseased arthritic mice (Collagen antibody-induced arthritis model), can migrate toward the inflamed synovia, usingin vivoimaging system (IVIS). Moreover, we show that these EVs strongly expresses glucose transporter 1 (mGLUT1) which in turn, improve their therapeutic potential to be loaded with anti-inflammatory drugs using glucose-coated gold nanoparticles (GNPs). Finally, we show that EVs derived from plasma of RA patients overexpresses αVβ3 integrin and taken up by LPS/TNFα-induced activated human synovial cell linein vitro.ConclusionOverall, we show the potential of autologous circulating EVs of RA patients to serves as natural nano-carrier for current FDA-approved drugs. We believe that this strategy will increase the specificity and efficiency of current treatment, therefore it will reduce side effects and will improve the quality of life of RA patients and potentially other autoimmune disease patients.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.