Simultaneous delivery of DNA vaccine and hydrophobic adjuvant using reducible polyethylenimine-functionalized graphene oxide for activation of dendritic cells

The activation and maturation of dendritic cells are critical in immunotherapy, and the potency of DCs is associated with high levels of antigen presentation on major histocompatibility complex (MHC) class I and II and the expression of costimulatory signals. Graphene oxide (GO) and its derivatives have many excellent physicochemical properties, including large and hydrophobic surface available for interacting with hydrophobic or aromatic drugs via π–π stacking forces, flexibility of the chemical modification on the surfaces, and capacity of DC activation. In this study, we designed a simple strategy to achieve the co-delivery of a DNA vaccine and hydrophobic immune adjuvant (R848) and to enhance the adjuvanticity of R848 via the synergistic effect of GO and R848. Thiolated low-molecular-weight polyethylenimine (TPEI1.8) was crosslinked with 4-aminothiophenol-modified GO (TGO) via the formation of disulfide bonds. Thus, TGO with its assembled TPEI1.8 could not only load R848 but also electrostatically interact with the DNA vaccine. Owing to the reducibility of the disulfide bond in the cellular environment, the DNA vaccine could be readily released. This system can significantly enhance the DNA transfection, the expression of the costimulatory signal, and the level of antigen presentation to MHC class I DCs for their activation and maturation.