siRNA-based nanotherapeutic approaches for targeted delivery in rheumatoid arthritis

Rheumatoid arthritis (RA), characterized as a systemic autoimmune ailment, predominantly results in substantial joint and tissue damage, affecting millions of individuals globally. Modern treatment modalities are being explored as the traditional RA therapy with non-specific immunosuppressive drugs showcased potential side effects and variable responses. Research potential with small interfering RNA (siRNA) depicted potential in the treatment of RA. These siRNA-based therapies could include genes encoding pro-inflammatory cytokines like TNF-α, IL-1, and IL-6, as well as other molecular targets such as RANK, p38 MAPK, TGF-β, Wnt/Fz complex, and HIF. By downregulating the expression of these genes, siRNA-based nanoformulations can attenuate inflammation, inhibit immune system dysregulation, and prevent tissue damage associated with RA. Strategies of delivering siRNA molecules through nanocarriers could be targeted to treat RA effectively, where specific genes associated with this autoimmune disease pathology can be selectively silenced. Additionally, simultaneous targeting of multiple molecular pathways may offer synergistic therapeutic benefits, potentially leading to more effective and safer therapeutic strategies for RA patients. This review critically highlights the in-depth pathology of RA, RNA interference-mediated molecular targets, and nanocarrier-based siRNA delivery strategies, along with the challenges and opportunities to harbor future solutions.