Mannosylated PEGylated-Polyethyleneimine as Efficient CpG Oligodeoxynucleotide Carriers for Efficient Dendritic Cell Targeting Delivery and Activation.

Abstract

CpG ODN acts as a 'pathogen-associated' molecular pattern that is recognized by intracellular Toll-like receptor 9 and can induce a robust dendritic cells (DCs) activation to against various diseases. However, the CpG ODN is restricted with critical defects of easily enzymolysis and negligible phagocytosis. To overcome these issues, a simpler and competent nanocarrier of mannose modified PEGylated branched PEI25k (PEI-PEG-Man) was designed to achieve excellent DCsspecific delivery of CpG. Nanoparticles of PEI-PEG-Man encapsulating CpG (PEI-PEG-Man@CpG) possessed elevated gene loading capacity, biological stability and admirable anti-enzymolysis ability. PEI-PEG-Man@CpG could be selectively uptake by DCs through a receptor-mediated endocytosis, which generates a potent immunostimulatory activity on bone marrow derived dendritic cells (BMDCs) evidenced by significantly upregulation of the pro and anti-inflammatory cytokines (TNF-α, IL-6) and the co-stimulatory molecules (CD40, CD80, CD86, and MHC class II) on BMDCs in vitro. More importantly, the results of in vivo targeting assay showed that PEI-PEG-Man@CpG nanoparticles could remarkably boost CpG accumulation in lymph lodes upon subcutaneous administration in C57BL/6 mice, which facilitated maturation of DCs and productions of anti-inflammatory cytokines. Our results suggested that PEI-PEG-Man@CpG nanoparticles, in the future, might function as a powerful vector for ex vivo engineering to promote DC targeting and maturation, which enhance vaccine efficiency against cancer or infectious disease.