title: Development of functionalized nanoparticles for vaccine delivery to dendritic cells: a mechanistic approach.
abstract: OBJECTIVE
  Produce biodegradable nanoparticles to target antigen-presenting cells (APCs) and evaluate their potential to be used as a vaccine delivery system.
  
  
  METHODS
  Untargeted PEGylated poly(d,l-lactic-co-glycolide)-based nanoparticles and mannose-grafted nanoparticles were formulated and physicochemically characterized. Immortalized and primary APCs were used to study nanoparticle internalization patterns. The endocytic pathways and intracellular trafficking followed by nanoparticles were also investigated.
  
  
  CONCLUSIONS
  Nanoparticles displayed mannose residues available for binding at the nanoparticle surface. Different nanoparticle internalization patterns by immortalized and primary APCs were verified. Macropinocytosis, clathrin-mediated endocytosis, caveolin- and lipid raft-dependent endocytosis are involved in nanoparticles internalization. Nanoparticles demonstrate both endolysosomal and cytosolic localizations and a tendency to accumulate nearby the endoplasmic reticulum.
  
  
  CONCLUSIONS
  The developed nanoparticles might drive antigens to be presented through MHC class I and II molecules to both CD8(+) and CD4(+) T cells, favoring a complete and coordinated immune response.
authors.affiliation: Faculdade de Farmácia, Universidade de Lisboa, Instituto de Investigação do Medicamento (iMed.ULisboa), Lisbon, Portugal.
authors.forename: Joana M
authors.initials: JM
authors.lastname: Silva
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Vandermeulen
authors.forename: Vanessa G
authors.initials: VG
authors.lastname: Oliveira
authors.forename: Sandra N
authors.initials: SN
authors.lastname: Pinto
authors.forename: Catarina
authors.initials: C
authors.lastname: Rodrigues
authors.forename: Ana
authors.initials: A
authors.lastname: Salgado
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Afonso
authors.forename: Ana S
authors.initials: AS
authors.lastname: Viana
authors.forename: Christine
authors.initials: C
authors.lastname: Jérôme
authors.forename: Liana C
authors.initials: LC
authors.lastname: Silva
authors.forename: Luis
authors.initials: L
authors.lastname: Graca
authors.forename: Véronique
authors.initials: V
authors.lastname: Préat
authors.forename: Helena F
authors.initials: HF
authors.lastname: Florindo
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000276:immunology; D063566:Biodegradable Plastics / Q000737:chemistry / Q000627:therapeutic use; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D016503:Drug Delivery Systems; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry; D014612:Vaccines / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D063566:Biodegradable Plastics; D014612:Vaccines; D011100:Polyglycolic Acid
keywords: PLGA; dendritic cells; immunotherapy; mannose receptor targeting; nanoparticles; vaccine delivery systems