Triamcinolone-Gold Nanoparticles Repolarize Synoviocytes and Macrophages in an Inflamed Synovium.

ABSTRACT

Understanding the crosstalk between synoviocytes and macrophages is very important for the development of strategies to regulate inflammatory responses in an inflamed synovium. Simultaneous regulation of the pro- and anti-inflammatory responses of synoviocytes and macrophages (repolarization) is critical for the treatment of arthritis. Thus, the immune regulatory functions of an ideal nanodrug should not only decrease the pro-inflammatory response but also effectively increase the anti-inflammatory response. In this study, crosstalk between synoviocytes and macrophages was found to be significantly involved in the activation and deactivation of inflammatory responses in the synovium. Interestingly, a developed triamcinolone-gold nanoparticle (Triam-AuNP) complex both decreased the pro-inflammatory responses and increased the anti-inflammatory responses of fibroblast-like synoviocytes (FLSs) and macrophages via repolarization of macrophages from the M1 to the M2 phenotype. In contrast, triamcinolone alone only decreased the pro-inflammatory responses of FLSs and macrophages without upregulating their anti-inflammatory responses. In vitro (human), ex vivo (human), and in vivo (mouse) analyses clearly indicated that Triam-AuNPs effectively regulated the expression of both pro- and anti-inflammatory cytokines in FLSs and effectively repolarized activity of macrophages in the inflamed synovium. Furthermore, Triam-AuNPs significantly promoted cartilage regeneration, whereas triamcinolone alone did not induce either FLS anti-inflammatory activity or macrophage repolarization.