Nanoparticles encapsulating antigenic peptides induce tolerogenic dendritic cells in situ for treating systemic lupus erythematosus.

Using Tetrahedral framework nucleic acids, we combined antigenic peptides to create the "DART" vaccine: DNA framework-Antigenic peptide-RNA modification-Targeting aptamer coupling. Generating antigen-specific tolerogenic dendritic cells (tolDCs), for systemic lupus erythematosus (SLE) is a potential therapeutic strategy for addressing compromised autoimmune tolerance. However, simple antigenic peptides degrade easily, lack specificity for delivery to dendritic cells (DCs), and cannot transform DCs to tolDCs. Therefore, this study aims to employ DART to generate tolDCs and compare DART-treated DCs to tolDCs. DART improved peptide stability, specifically targeted DCs, induced tolDCs in situ, and showed promising outcomes in mitigating SLE symptoms in the MRL/lpr mouse model. DART effectively normalized the plasma cytokine levels, glomerulonephritis, and joint lesions in MRL/lpr mice. These findings highlight the potential of the DART vaccine to induce transformation of DCs to tolDCs and address SLE symptoms, suggesting novel therapeutic utility. These findings may advance vaccine design for various autoimmune diseases.