Abstract
Objectives:This study was aimed at developing DNA delivery systems by exploiting MHC‐binding motifs. We tested the hypothesis that particles guided by MHC class II ligands can enhance uptake of oligodeoxynucleotides (ODN) into dendritic cells (DCs).Methods:Particles fabricated from PLGA or polystyrene (PS) were coated with the peptide VHA (amino acid sequence VHASHAVHAAHAVHA) which fulfills the binding motif of the murine class II MHC molecule I‐Ad. FITC‐labeled NF‐κB decoy ODN were condensed on the surface of the particles via the cationic peptide O10H6. DCs derived from BALB/c (I‐Ad) and C57BL/6 (I‐Ab) mice were used as the surrogate target and control, respectively.Results:VHA‐anchored particles carrying the decoy were found to be in the nano‐sized range (120–400nm). VHA‐mediated ODN uptake was demonstrated using flow cytometry (2‐fold higher MFI in I‐Ad vs. I‐Ab DCs). The uptake in BALB/c DCs was blocked by an anti‐I‐Ad antibody. Lysotracker staining showed lysosomal escape of DNA in cells. BALB/c DCs treated with VHA‐directed ODN show decreased sensitivity to LPS as measured by CD86 expression (2‐fold, n=3 p<0.05). Differential IFN‐γ production (34%±5%, n=4, p<0.05) upon stimulation was observed in VHA‐guided ODN exposed I‐Ad DCs compared to I‐Ab DCs.Conclusion:The results support the concept that MHC class II ligands can be used to facilitate delivery of DNA into DCs.
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