Hybrid nanovaccine for the co-delivery of the mRNA antigen and adjuvant.

For efficient cancer vaccines, the antitumor function largely relies on cytotoxic T cells, whose activation can be effectively induced via antigen-encoding mRNA, making mRNA-based cancer vaccines an attractive approach for personalized cancer therapy. While the liposome-based delivery system enables the systemic delivery and transfection of mRNA, incorporating an adjuvant that is non-lipid like remains challenging, although the co-delivery of mRNA (antigen) and effective adjuvant is key to the activation of the cytotoxic T cells. This is because the presence of an adjuvant is important for dendritic cell maturation-another necessity for cytotoxic T cell activation. In the present work, we designed a poly (lactic-co-glycolic acid) (PLGA)-core/lipid-shell hybrid nanoparticle carrier for the co-delivery of mRNA and gardiquimod (adjuvant that cannot be incorporated into the lipid shell). We demonstrated in the present work that the co-delivery of mRNA and gardiquimod led to the effective antigen expression and DC maturation in vitro. The intravenous administration of the hybrid nanovaccine resulted in the enrichment of mRNA expression in the spleen and a strong immune response in vivo. The simultaneous delivery of the antigen and adjuvant both spatially and temporally via the core/shell nanoparticle carrier is found to be beneficial for tumor growth inhibition.