title: Uptake of biodegradable poly(γ-glutamic acid) nanoparticles and antigen presentation by dendritic cells in vivo.
abstract: Poly(γ-glutamic acid) (γ-PGA) nanoparticles (NPs) carrying antigens have been shown to induce potent antigen-specific immune responses. However, in vivo delivery of γ-PGA NPs to dendritic cells (DCs), a key regulator of immune responses, still remains unclear. In this study, γ-PGA NPs were examined for their uptake by DCs and subsequent migration from the skin to the regional lymph nodes (LNs) in mice. After subcutaneous injection of fluorescein 5-isothiocyanate (FITC)-labeled NPs or FITC-ovalbumin (OVA)-carrying NPs (FITC-OVA-NPs), DCs migrated from the skin to the LNs and maturated, resulting in the upregulation of the costimulatory molecules CD80 and CD86 and the chemokine receptor CCR7. However, the migrated DCs were not detected in the spleen. FITC-OVA-NPs were found to be taken up by skin-derived CD103(+) DCs, and the processed antigen peptides were cross-presented by the major histocompatibility complex (MHC) class I molecule of DCs. Furthermore, significant activation of antigen-specific CD8(+) T cells was observed in mice immunized with OVA-carrying NPs (OVA-NPs) but not with OVA alone or OVA with an aluminum adjuvant. The antigen-specific CD8(+) T cells were induced within 7 days after immunization with OVA-NPs. Thus, γ-PGA NPs carrying various antigens may have great potential as an antigen-delivery system and vaccine adjuvant in vivo.
authors.affiliation: Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-0544, Japan ; Core Research for Evolutional Science and Technology (CREST), the Japan Science and Technology Agency (JST), Tokyo 150-0002, Japan.
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Uto
authors.affiliation: Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-0544, Japan ; Core Research for Evolutional Science and Technology (CREST), the Japan Science and Technology Agency (JST), Tokyo 150-0002, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Toyama
authors.affiliation: Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-0544, Japan ; Core Research for Evolutional Science and Technology (CREST), the Japan Science and Technology Agency (JST), Tokyo 150-0002, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Nishi
authors.affiliation: Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Suita 565-0871, Japan ; Core Research for Evolutional Science and Technology (CREST), the Japan Science and Technology Agency (JST), Tokyo 150-0002, Japan.
authors.forename: Takami
authors.initials: T
authors.lastname: Akagi
authors.affiliation: Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Suita 565-0871, Japan ; Core Research for Evolutional Science and Technology (CREST), the Japan Science and Technology Agency (JST), Tokyo 150-0002, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Shima
authors.affiliation: Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Suita 565-0871, Japan ; Core Research for Evolutional Science and Technology (CREST), the Japan Science and Technology Agency (JST), Tokyo 150-0002, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Akashi
authors.affiliation: Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-0544, Japan ; Core Research for Evolutional Science and Technology (CREST), the Japan Science and Technology Agency (JST), Tokyo 150-0002, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Baba
keywords: Dendritic cell; Drug delivery; Immune response; Nanoparticle; Vaccine