Au Clusters Treat Rheumatoid Arthritis with Uniquely Reversing Cartilage/Bone Destruction

Abstract

Super-small nanoclusters may intrinsically trigger specific molecular pathway for disease treatment in vitro/vivo. To prove the hypothesis the super-small nanoclusters, e.g., Au clusters, are directly used to treat rheumatoid arthritis (RA) in vitro/vivo. RA is a chronic autoimmune disease that is characterized by the inflammation of joints and the unreversible destruction of the cartilage/bone. Au clusters significantly suppress lipopolysaccharide (LPS)-induced proinflammatory mediator production in the murine macrophage cell line by inhibiting the signaling pathways that regulate the major proinflammatory mediator genes. In preclinical rat RA studies, Au clusters strongly prevent type II collagen-induced rat RA without systemic side effects. Compared with the clinical first-line anchored anti-RA drug, methotrexate, Au clusters equally inhibit inflammation in vivo. Type II collagen-induced rat RA is characterized with the destruction of cartilage/bone; treatment with Au clusters reverses the destruction of cartilage/bone to its normal state. This is because Au clusters directly inhibit receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and function through the downregulation of osteoclast-specific genetic marker expression. However the methotrexate almost has no positive effect for this key issue in rat RA therapy. These data prove that the super-small nanoclusters, e.g., Au clusters, could be a novel candidate nanodrug for RA treatment.