Mesenchymal Stem Cell Conjugated with Triamcinolone Loaded Gold Nanoparticles Attenuates Rheumatoid Arthritis

Unfortunately, conventional therapy for rheumatoid arthritis (RA), which is an autoimmune and inflammatory disease, was not enough to attenuate the RA patient with severe inflammatory symptoms. Mesenchymal stem cells (MSCs) are considered as a promising regenerative therapy for the treatment of RA due to their regenerative activity and ability to migrate toward damaged tissues, but the insufficient anti-inflammatory efficacy limited MSC application in various stages of RA patients. In this aspect, the combination of nano-drugs and MSCs can increase the anti-inflammatory response at the inflamed joints, and the severe stages of RA can be recovered. In this study, the inflammation-mediated education process without genetic engineering enhanced the migration ability of MSCs to inflamed joints. Star-shaped gold NPs (AuStar: AuS) were synthesized with the conjugation of Triamcinolone (TA), a glucocorticoid widely used for inflammatory disease. AuS-TA stably conjugated on the surface of MSCs, and inflammation-educated MSCs with conjugation of triamcinolone-loaded gold nanostar (Edu-MSCs/AuS-TA) elicited remarkable attenuation of RA in collagen-induced arthritis (CIA) mouse model. Furthermore, photothermal therapy (PTT) with the irradiation of near-infrared (NIR) laser on inflamed joints showed the maximized efficacy of the anti-inflammatory response for the treatment of the severe stage of the CIA model. Specifically, Edu-MSCs/AuS-TA promoted the repolarization of macrophages from the M1 to the M2 phenotype and decreased the recruitment of neutrophils in joints. Additionally, Edu-MSCs/AuS-TA significantly decreased pain and increased general locomotor activity levels and cartilage regeneration.