Cationic nanoparticles for delivery of CpG oligodeoxynucleotide and ovalbumin: In vitro and in vivo assessment

The use of cationic nanoparticles (NPs) for enhancing the delivery of an immunostimulatory adjuvant, CpG ODN, and model antigen, OVA to dendritic cells was investigated in these studies. In vitro studies demonstrated that NPs were taken up efficiently by bone-marrow derived dendritic cells (BMDDCs), with approximately 70% of the NPs found associated with cells over 12 hr. The presence of NPs intracellulary in DCs was confirmed by confocal microscopy. NPs alone did not cause release of IL-12 from BMDDCs; however, CpG-coated NPs (CpG/NPs) resulted in the release of IL-12 and the cytokine levels were greater using the NPs than GpG alone. Adoptive transfer experiments using OT-1 TCR transgenic T cells demonstrated higher proliferation of the OT-1 cells using OVA-coated NPs (OVA/NPs) compared to OVA alone, especially at lower doses of OVA. Taken together, the in vitro and in vivo data suggest that nanoparticles can enhance the uptake of antigen or immunostimulatory adjuvant into antigen presenting cells such as dendritic cells, and facilitate MHC class I restricted antigen presentation to CD8⁺ T cells. Moreover, in vivo immunization studies in BALB/ c mice demonstrated that significant enhancements in humoral immune responses to OVA can be obtained using CpG-coated NPs compared to either CpG or NPs alone.