Current treatment for rheumatoid arthritis (RA), a chronic autoimmune disorder characterized by synovial joint inflammation leading to cartilage destruction, focuses on pain relief rather than complete disease remission. A potential target for securing disease remission is the inflammatory cytokine, tumor necrosis factor-α (TNF-α). TNF-α is produced by macrophages that occur at high abundance in the inflamed membranes and has been shown to influence the progression of synovial damage. Silencing TNF-α expression using small interfering RNA (siRNA) has been explored as a therapeutic strategy for RA treatment.
The preferred method of administering siRNA-based therapeutics is by local delivery, which provides direct access to the macrophage cells. The authors evaluate poly(DL-lactic-co-glycolic acid) (PLGA) nanoparticles as a carrier system for efficient delivery of siRNA molecules across the plasma membrane of the macrophages and into the cytosol. Using Dicer-substrate siRNA (DsiRNA; provided by IDT) targeted at TNF-α, they show that DsiRNA-loaded PLGA nanoparticles mediate dose-dependent silencing of TNF-α in vitro. They also demonstrate the effectiveness of using MRI to monitor disease progression by showing reduction of disease activity in vivo.