title: Protein direct delivery to dendritic cells using nanoparticles based on amphiphilic poly(amino acid) derivatives.
abstract: Induction of an adaptive immune response by vaccination is possible for a broad range of infectious diseases or cancers. Antigen-loaded polymeric nanoparticles have recently been shown to possess significant potential as vaccine delivery systems and adjuvants. Here we demonstrate the use of nanoparticles composed of amphiphilic poly(amino acid) derivatives as vaccine adjuvants. We prepared protein-loaded, biodegradable nanoparticles composed of hydrophobically modified poly(gamma-glutamic acid) (gamma-PGA). gamma-PGA hydrophobic derivatives (gamma-hPGA) formed 200 nm-sized nanoparticles in water. The protein-encapsulated gamma-hPGA nanoparticles were efficiently taken up by immature dendritic cells (iDCs). Interestingly, the nanoparticle uptake by iDCs induced DC maturation. The immunization with human immunodeficiency virus (HIV)-1 gp120-encapsulated nanoparticles strongly induced antigen-specific cellular immunity. These results suggest that antigen-loaded gamma-hPGA nanoparticles provide a novel delivery tool for vaccination against viral infections or tumors. This system has potential application as a universal delivery system for protein-based vaccines capable of inducing cytotoxic T lymphocyte (CTL).
authors.affiliation: Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita 565-0871, Japan.
authors.forename: Takami
authors.initials: T
authors.lastname: Akagi
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Uto
authors.forename: Masanori
authors.initials: M
authors.lastname: Baba
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Akashi
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D003713:Dendritic Cells / Q000276:immunology*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010047:Ovalbumin / Q000276:immunology; D010316:Particle Size; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011506:Proteins / Q000737:chemistry* / Q000648:ultrastructure
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D011108:Polymers; D011506:Proteins; C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid; D010047:Ovalbumin