Application of Magnesium Pyrophosphate-Based Sponge-Like Microparticles to Enhance the Delivery Efficiency and Adjuvant Effects of Polyriboinosinic-Polyribocytidylic Acid in Immune Cells.

ABSTRACT

The magnesium pyrophosphate particle (MgPP) is a unique and safe carrier that is prepared by simply mixing magnesium chloride and sodium pyrophosphate. In this study, we investigated whether MgPP can be used to deliver nucleic acid-based adjuvants to immune cells. Polyriboinosinic-polyribocytidylic acid (polyIC), a ligand for toll-like receptor 3, was selected as a model nucleic acid-based adjuvant. PolyIC-loaded MgPP (polyIC-MgPP) was prepared by adding polyIC during the MgPP preparation process. Efficient loading of polyIC into MgPP was confirmed by measuring the absorbance at 260 nm after disruption of polyIC-MgPP by ethylenediaminetetraacetic acid. Scanning electron microscopy revealed that both MgPP and polyIC-MgPP had a unique sponge-like shape with a diameter of approximately 1 µm. PolyIC-MgPP was more efficiently taken up by toll-like receptor 3-positive RAW264.7 cells than naked polyIC, and its uptake stimulated increased tumor necrosis factor-α production. When the presentation of ovalbumin (OVA), a model antigen, was evaluated after the addition of OVA along with naked polyIC or polyIC-MgPP to mouse dendritic DC2.4 cells, polyIC-MgPP substantially increased OVA presentation. These results indicate that MgPP is a useful delivery vehicle for polyIC and that polyIC-MgPP is an effective immune cell adjuvant.