Targeted delivery of Prussian blue modified exosomes to CD90-expressing synovial fibroblasts for Rheumatoid arthritis immunotherapy

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation and joint destruction. Current therapeutic approaches face challenges such as systemic toxicity and insufficient targeting. Exosomes have emerged as novel carriers for RA treatment due to their inherent targeting capability, low immunogenicity, and efficient delivery capacity. This study aimed to construct a targeted delivery system (CD90-exo@PB) based on CD90-modified exosomes (CD90-exo) loaded with Prussian blue nanoparticles (PB) for specific therapy of RA. In vitro experiments demonstrated that CD90-exo@PB could be efficiently internalized by activated synovial fibroblasts (aFLS), significantly inhibiting aFLS migration through reduction of pro-inflammatory cytokines. In a collagen-induced arthritis (CIA) mouse model, near-infrared fluorescence imaging revealed targeted accumulation of CD90-exo@PB in inflamed joints, accompanied by effective alleviation of joint swelling. Mechanistic studies indicated that the therapeutic efficacy was closely associated with downregulation of pro-inflammatory cytokines. The developed CD90-exo@PB system integrates active targeting with antioxidant synergistic effects, providing an innovative strategy for precision therapy of RA with significant clinical translation potential.