Amphiphilic Poly(Amino Acid) Nanoparticles Induce Size-Dependent Dendritic Cell Maturation

Size-regulated amphiphilic poly(amino acid) nanoparticles (NPs) composed of poly(gamma-glutamic acid) (gamma-PGA) and the hydrophobic amino acid derivative, L-phenylalanine ethyl ester (Phe) are prepared to evaluate the effects of particle size on dendritic cell (DC) uptake of NPs and their immune stimulatory activities as delivery carriers and adjuvants. The size of the Phe-conjugated gamma-PGA NPs (gamma-PGA-Phe NPs) is easily controlled by regulating the aggregated gamma-PGA-Phe numbers. Each of the differently sized gamma-PGA-Phe NPs could efficiently encapsulate ovalbumin (OVA), and the amount of encapsulated OVA per milligram of NPs is almost the same despite the differences in size. The DC uptake of small NPs is lower than for the larger NPs, but the effect of DC activation by NPs is high in the small sizes. The DC activation is significantly affected by the size of the NPs, which suggests that not only the uptake process of the NPs, but also the surface interactions between the NPs and DCs, is important for the induction of DC maturation. The precisely size-controllable gamma-PGA-Phe NPs have significant potential as an antigen carrier and vaccine adjuvant. These results should provide guidelines for adjuvant design in the development of an effective vaccine.