title: Size effect of amphiphilic poly(γ-glutamic acid) nanoparticles on cellular uptake and maturation of dendritic cells in vivo.
abstract: We prepared size-regulated nanoparticles (NPs) composed of amphiphilic poly(γ-glutamic acid) (γ-PGA). In this study, 40, 100 and 200 nm γ-PGA-graft-l-phenylalanine ethylester (γ-PGA-Phe) NPs were employed. The size of NPs significantly influenced the uptake and activation behaviors of antigen-presenting cells (APCs). When 40 nm γ-PGA-Phe NPs were applied to these cells in vitro, they were highly activated compared with 100 and 200 nm NPs, while cellular uptake was size dependent. The size of the γ-PGA-Phe NPs also significantly affected their migration to the lymph nodes and uptake behavior of NPs by dendritic cells (DCs) in vivo. The 40 nm γ-PGA-Phe NPs migrated more rapidly to the lymph nodes and were taken up by a greater number of DCs compared with 100 and 200 nm NPs. On the other hand, when the amount of γ-PGA-Phe NPs taken up per DC was evaluated, it was higher for 100 and 200 nm NPs than for 40 nm NPs, which suggests that the larger γ-PGA-Phe NPs can deliver a large amount of antigen to a single DC compared with smaller NPs. Furthermore, when examined the maturation of DCs in lymph nodes, 40 nm γ-PGA-Phe NPs efficiently stimulated DCs. These results suggest that the activation, uptake behavior by APCs, migration to lymph nodes, and DC maturation can be controlled by the size of γ-PGA-Phe NPs.
authors.affiliation: Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita 565-0871, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi Center Building, 4-1-8 Honcho, Kawaguchi 332-0012, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Shima
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Uto
authors.forename: Takami
authors.initials: T
authors.lastname: Akagi
authors.forename: Masanori
authors.initials: M
authors.lastname: Baba
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Akashi
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects*; D005260:Female; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013194:Staining and Labeling; D013501:Surface-Active Agents / Q000737:chemistry*
chemical_list: D013501:Surface-Active Agents; C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid
keywords: Dendritic cells; Lymph nodes; Nanoparticles; Particle size; Vaccine