PLGA Nanoparticles Coated with Activated Dendritic Cell Membrane Can Prolong Protein Expression and Improve the Efficacy of mRNA

Abstract

In future, mRNA drugs likely play crucial roles in vaccines and protein replacement therapy etc. Lipid nanoparticles (LNPs) are the only formulation approved for mRNA delivery. However, in cancer vaccine, the mRNA encapsulated in LNP can only encode limited (20–40) tumor antigens. Due to highly heterogeneous of tumor cells and tumor antigens, including more diverse antigens could improve the efficacy of cancer vaccines. Including both strong immunogenic antigens and more diverse antigens could maximize the efficacy of cancer vaccines. Herein, poly (lactic-co-glycolic acid) (PLGA) nanoparticles and activated dendritic cell membrane were designed as mRNA delivery platforms, which possess merits such as prolonged protein expression, lyophilized formulation, and greater efficacy etc. Dendritic cells were activated with particles loading whole tumor antigens which can activate broad range antigen-specific T cells. The sustained release of mRNA in PLGA nanoparticles can significantly prolong protein expression in APCs, and lyophilization improved the stability of mRNA formulation. Compared with LNPs, these nanovaccines significantly improved the therapeutic efficacy of mRNA. In addition, tumor antigen-specific T cells in mice treated with nanovaccines was significantly greater than that treated with LNPs. Overall, a new platform for delivering mRNA was demonstrated, that can prolong protein expression and have better efficacy.