title: Development of tripartite polyion micelles for efficient peptide delivery into dendritic cells without altering their plasticity.
abstract: For many years, a great deal of interest has been focusing on the optimization of peptide presentation by dendritic cells (DCs) using peptide-encapsulated particles, in order to enhance the immune response. Nowadays, DCs are also known to be involved in peripheral tolerance, inducing anergy or regulatory T lymphocytes. To preserve the plasticity of DCs, we formulated non-cytotoxic pH-sensitive polyion complex micelles based on an original tripartite association of polymethacrylic acid-b-polyethylene oxide, poly-L-lysine and fluorescent-peptide: OVAFITC peptide, as a model drug. We demonstrated that the OVAFITC peptide was successfully entrapped into the micelles, released into DC endosomes thanks to the pH-sensitivity property of the micelles, and efficiently loaded onto MHC class II molecules. The phenotype as well as the cytokinic secretion profile of the mature and immature DCs loaded with peptide-encapsulated micelles was unaltered by the tripartite polyion micelles. The efficient loading of the peptide by immature and mature DCs was shown by the in vitro proliferation of OVA-specific transgenic T cells. Therefore, the present results show that the tripartite polyion complex micelles can be used as efficient peptide vectors immunogically inert for ex vivo DCs engineering without modifying their intrinsic immune plasticity.
authors.affiliation: Institut Charles Gerhardt Montpellier, UMR 5253 CNRS-ENSCM-UM2-UM1, Equipe MACS, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex 5, France.
authors.forename: Ariane
authors.initials: A
authors.lastname: Boudier
authors.forename: Anne
authors.initials: A
authors.lastname: Aubert-Pouëssel
authors.forename: Naila
authors.initials: N
authors.lastname: Mebarek
authors.forename: Alain
authors.initials: A
authors.lastname: Chavanieu
authors.forename: Julie
authors.initials: J
authors.lastname: Quentin
authors.forename: Delphine
authors.initials: D
authors.lastname: Martire
authors.forename: Hassan
authors.initials: H
authors.lastname: Boukhaddaoui
authors.forename: Corine
authors.initials: C
authors.lastname: Gérardin
authors.forename: Christian
authors.initials: C
authors.lastname: Jorgensen
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Devoisselle
authors.forename: Pascale
authors.initials: P
authors.lastname: Louis-Plence
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bégu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology* / Q000637:transplantation; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008823:Micelles; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000378:metabolism; D011109:Polymethacrylic Acids / Q000008:administration & dosage / Q000378:metabolism
chemical_list: D008823:Micelles; D010446:Peptide Fragments; D011109:Polymethacrylic Acids; C030613:polymethacrylic acid; D011092:Polyethylene Glycols; D010047:Ovalbumin