Developing cerium modified gold nanoclusters for the treatment of advanced-stage rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune-mediated inflammatory disease that seriously threatens patients' life. Different stages of RA require different treatments, but the accurate classification of the RA remains challenging. Herein, we conducted an in-depth study of 73 RA patients to investigate RA development. CD 19, a biomarker of B cell dysfunction, was found to be strongly associated with the development of severe symptoms. On the other hand, CD19 was significantly reduced, when effective clinical treatment relieved the symptoms. Therefore, it is proposed that B cell-inducing factors are important for the development of RA to the advanced stage and can be used to assist in the accurate classification of RA development. Furthermore, we speculated that drugs that could properly modulate B cells might have efficacy in advanced-stage RA. From this perspective, R-dihydrolipoic acid (R-DHLA)-stabilized cerium-modified gold nanoclusters (AuNCs) (R-DHLA-AuNCs-Ce) (∼3.4 ​nm) were developed for comprehensive treatment of advanced-stage RA. According to our established rat models of collagen-induced arthritis (CIA), R-DHLA-AuNCs-Ce restored the comprehensive changes of cytokines to a normal state by regulating B cell activity within 24 ​h. Furthermore, the immune responses elicited by B cells were memory-suppressed after detachment from R-DHLA-AuNCs-Ce and the advanced symptoms of RA in CIA rats were successfully reversed to a healthy state. Compared to clinical drugs such as methotrexate (MTX) and etanercept, R-DHLA-AuNCs-Ce were found to more efficiently suppress B cell immunity mitigating advanced-stage RA.