Nanoparticle-facilitated delivery of BAFF-R siRNA for B cell intervention and rheumatoid arthritis therapy

Abstract The present study was designed to explore the effects of B-cell activating factor receptor (BAFF-R) siRNA encapsulated nanoparticles on collagen-induced arthritis (CIA). BAFF-R siRNA encapsulated nanoparticles (NP-siBAFF-R) were constructed using a double emulsion method and was characterized by dynamic light scattering and transmission electron microscopy. Cellular uptake of nanoparticles was determined using flow cytometry. The CIA mouse model was established and the mice were intravenously injected with nanoparticles. NP-siBAFF-R effectively decreased the expression of BAFF-R in B cells and facilitated the delivery of siRNA into B cells. Treatment of NPsiBAFF-R ameliorated rheumatoid arthritis (RA) symptoms in the CIA mouse model via decreasing the arthritis score, mean ankle diameter, the levels of anti-collagen IgG in serum and increasing the expression of collagen type II and osteocalcin in dissected joint tissues. Additionally, treatment of NPsiBAFF-R decreased the percentage and number of B cells and inhibited the production of pro-inflammatory cytokines in RA mice. These results demonstrate that NP-siBAFF-R may provide an effective strategy for RA treatment.