Lipid Nanoparticle-Mediated Lymphatic Delivery of Immunostimulatory Nucleic Acids

Lymphatic delivery of a vaccine can be achieved using a dendritic cell (DC)-targeted delivery system that can cause DC to migrate to lymph nodes upon activation by an adjuvant. Here, we designed a mannose-modified cationic lipid nanoparticle (M-NP) to deliver the nucleic acid adjuvant, polyinosinic:polycytidylic acid (PIC). PIC-loaded M-NP (PIC/M-NP) showed stable lipoplexes regardless of the ligand ratio and negligible cytotoxicity in bone marrow-derived DC. DC uptake of PIC/M-NP was demonstrated, and an increased mannose ligand ratio improved DC uptake efficiency. PIC/M-NP significantly promoted the maturation of bone marrow-derived DC, and local injection of PIC/M-NP to mice facilitated lymphatic delivery and activation (upon NP uptake) of DC. Our results support the potential of PIC/M-NP in delivering a nucleic acid adjuvant for the vaccination of antigens.