Lymph nodes-targeted nano-prodrug for precise B cell immunoregulation to prevent collagen-induced arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease marked by progressive joint destruction and deformities, which are irreversible once they develop. If the disease can be prevented in the preclinical stage, it may significantly reduce the rate of RA incidence and disability. However, insufficient attention has been paid to RA prevention. Herein, we proposed a nano-prodrug delivery (HC-IBR) to modulate the B cell immune response in lymph nodes (LNs) during the preclinical phase of RA. The HC-IBR was constructed by self-assembly of hyaluronic acid (HA) bearing cyanine7 (Cy7) and bruton tyrosine kinase inhibitor ibrutinib (IBR). The HC-IBR effectively targeted and specifically accumulated in LNs and further controlled IBR drug release under light irradiation. HC-IBR plus laser exhibited better efficiency in inhibition of antigen-presenting B cell and germinal center to control the development of joint inflammation in mice with collagen induced arthritis. This study provides a potential novel strategy for RA prevention by precise and localized B cell immunoregulation.