Hydrophobic chain modified low molecular weight polyethylenimine for efficient antigen delivery†
The development of new therapeutic vaccines for the efficient induction of cellular immunity by antigen cross-presentation in antigen-presenting cells, especially dendritic cells, is regarded as a promising approach to prime antigen-specific T cell responses and to destroy tumor cells. We synthesized low molecular weight polyethylenimine (C12-PEI) with a modified hydrophobic lipid chain by the direct coupling of 1-bromododecane with low molecular weight polyethylenimine (MW 423 Da) in a 2 : 1 molar ratio. This was bound with model antigen ovalbumin (OVA) to form sphere-like polyplex nanoparticles (size 158–302 nm; zeta potential −18.4 to −13.1 mV) by electrostatic interaction at an C12-PEI/OVA weight ratio of 0.03–0.08. The in vitro cytotoxicity of the C12-PEI/OVA nanoparticles was strongly dependent on the weight ratio of the C12-PEI and OVA. The antigen cross-presentation effect (IL-2 secretion) of the C12-PEI/OVA polyplexes was also dependent on the weight ratio. Optimized cross-presentation was achieved on the C12-PEI/OVA-0.07/1 polyplexes, which was 5.3-fold higher than that of the free OVA solution and 1.9-fold higher than that of the PEI/OVA polyplexes. The intracellular distribution of the C12-PEI/rhodamine-labeled OVA polyplexes demonstrated the lysosome localization effect. These results indicated that the synthesized C12-PEI cationic polymer with a modified hydrophobic lipid chain could potentially be used as a therapeutic vaccine carrier for delivery of the OVA antigen.