Engineered DNA nanodrugs alleviate inflammation in inflammatory arthritis

Rheumatoid arthritis (RA) is an autoimmune disease featured with chronic joint inflammation. Suppression of inflammation is critical to RA treatment and joint protection. In this study, DNA nanodrugs are prepared via the conjugation of NF-κB decoy oligodeoxynucleotides (dODNs) and VCAM-1 targeted peptides (P) onto self-assembled DNA tetrahedrons (TDs). Physicochemical properties of DNA nanodrugs are characterized using atomic force microscopy (AFM), gel electrophoresis and Fourier Transform Infrared Spectrometer (FTIR). Cytotoxicity, cellular uptake and anti-inflammatory efficacy of DNA nanodrugs are evaluated in vitro. Clinical arthritis index, inflammatory proteins in serum and joint pathophysiology are also investigated in vivo. TD-P-dODN possesses one dODN and one P and exhibits faster and higher cellular uptake by inflammatory cells compared with free dODNs. TD-P-dODN also significantly reduce inflammatory proteins in cells and adjuvant induced arthritis (AIA) mice. Reduced clinical arthritis index and improved joint rehabilitation are also achieved by TD-P-dODN treatment. This study demonstrates that an engineered DNA nanodrug (TD-P-dODN) enhances the efficacy of nucleic acid drugs and represents a promising strategy for RA treatment.