title: Spontaneous Protein Adsorption on Graphene Oxide Nanosheets Allowing Efficient Intracellular Vaccine Protein Delivery.
abstract: Nanomaterials hold potential of altering the interaction between therapeutic molecules and target cells or tissues. High aspect ratio nanomaterials in particular have been reported to possess unprecedented properties and are intensively investigated for their interaction with biological systems. Graphene oxide (GOx) is a water-soluble graphene derivative that combines high aspect ratio dimension with functional groups that can be exploited for bioconjugation. Here, we demonstrate that GOx nanosheets can spontaneously adsorb proteins by a combination of interactions. This property is then explored for intracellular protein vaccine delivery, in view of the potential of GOx nanosheets to destabilize lipid membranes such as those of intracellular vesicles. Using a series of in vitro experiments, we show that GOx nanosheet adsorbed proteins are efficiently internalized by dendritic cells (DCs: the most potent class of antigen presenting cells of the immune system) and promote antigen cross-presentation to CD8 T cells. The latter is a hallmark in the induction of potent cellular antigen-specific immune responses against intracellular pathogens and cancer.
authors.affiliation: Department of Pharmaceutics, Ghent University , Ottergemsesteenweg 460, 9000 Ghent, Belgium.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: VIB Inflammation Research Center, Ghent University , Technologiepark 927, 9052 Zwijnaarde, Belgium.|Department of Respiratory Medicine, University Hospital Ghent , De Pintelaan 185, 9000 Ghent, Belgium.
authors.forename: Kaat
authors.initials: K
authors.lastname: Fierens
authors.affiliation: Department of Pharmaceutics, Ghent University , Ottergemsesteenweg 460, 9000 Ghent, Belgium.
authors.forename: Zhiyue
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, Ghent University , Ottergemsesteenweg 460, 9000 Ghent, Belgium.
authors.forename: Nane
authors.initials: N
authors.lastname: Vanparijs
authors.affiliation: VIB Inflammation Research Center, Ghent University , Technologiepark 927, 9052 Zwijnaarde, Belgium.|Department of Respiratory Medicine, University Hospital Ghent , De Pintelaan 185, 9000 Ghent, Belgium.
authors.forename: Martijn J
authors.initials: MJ
authors.lastname: Schuijs
authors.affiliation: Department of Pharmaceutics, Ghent University , Ottergemsesteenweg 460, 9000 Ghent, Belgium.
authors.forename: Katleen
authors.initials: K
authors.lastname: Van Steendam
authors.affiliation: Institute for Bioengineering of Catalonia , Carrer de Baldiri Reixac, 10, 08028 Barcelona, Spain.
authors.forename: Natàlia
authors.initials: N
authors.lastname: Feiner Gracia
authors.affiliation: Department of Respiratory Medicine, University Hospital Ghent , De Pintelaan 185, 9000 Ghent, Belgium.|Department of Biomedical Molecular Biology, Ghent University , Technologiepark 927, 9052 Zwijnaarde, Belgium.
authors.forename: Riet
authors.initials: R
authors.lastname: De Rycke
authors.affiliation: Department of Pharmaceutical Analysis, Ghent University , Ottergemsesteenweg 460, 9000 Ghent, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: De Beer
authors.affiliation: Department of Biomedical Molecular Biology, Ghent University , Technologiepark 927, 9052 Zwijnaarde, Belgium.
authors.forename: Ans
authors.initials: A
authors.lastname: De Beuckelaer
authors.affiliation: Department of Biomedical Molecular Biology, Ghent University , Technologiepark 927, 9052 Zwijnaarde, Belgium.
authors.forename: Stefaan
authors.initials: S
authors.lastname: De Koker
authors.affiliation: Department of Pharmaceutics, Ghent University , Ottergemsesteenweg 460, 9000 Ghent, Belgium.
authors.forename: Dieter
authors.initials: D
authors.lastname: Deforce
authors.affiliation: Institute for Bioengineering of Catalonia , Carrer de Baldiri Reixac, 10, 08028 Barcelona, Spain.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Albertazzi
authors.affiliation: Department of Biomedical Molecular Biology, Ghent University , Technologiepark 927, 9052 Zwijnaarde, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Grooten
authors.affiliation: VIB Inflammation Research Center, Ghent University , Technologiepark 927, 9052 Zwijnaarde, Belgium.|Department of Respiratory Medicine, University Hospital Ghent , De Pintelaan 185, 9000 Ghent, Belgium.
authors.forename: Bart N
authors.initials: BN
authors.lastname: Lambrecht
authors.affiliation: Department of Pharmaceutics, Ghent University , Ottergemsesteenweg 460, 9000 Ghent, Belgium.
authors.forename: Bruno G
authors.initials: BG
authors.lastname: De Geest
mesh_terms: D000327:Adsorption; D003713:Dendritic Cells / Q000187:drug effects; D016503:Drug Delivery Systems; D006108:Graphite / Q000737:chemistry* / Q000627:therapeutic use; D006801:Humans; D049329:Nanostructures / Q000737:chemistry / Q000627:therapeutic use; D010087:Oxides; D011506:Proteins / Q000737:chemistry* / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects; D014612:Vaccines / Q000737:chemistry* / Q000627:therapeutic use
chemical_list: D010087:Oxides; D011506:Proteins; D014612:Vaccines; D006108:Graphite
keywords: dendritic cells; graphene oxide; nanosheets; protein; vaccines