title: Soluble and immobilized graphene oxide activates complement system differently dependent on surface oxidation state.
abstract: Graphene oxide (GO) is believed to become applicable in biomedical products and medicine, thereby necessitating appropriate safety evaluation dependent on their applications and the route of administration. We have examined the effect of GO form (in solution versus immobilized) and oxidation state on two related elements of innate immunity: the complement system and interleukin-6 (IL-6) release in human blood. In solution, there was a decrease in GO-mediated complement activation with decreasing surface oxygen content (and altered oxygen functionality), whereas with immobilized GO complement response were reversed and increased with decreasing oxygen content. GO solutions, at concentrations below complement activating threshold, did not induce IL-6 release from human blood leukocytes, and further dampened lipopolysaccharide-induced IL-6 release in the whole blood. The latter effect became more profound with GO's having higher oxygen content. This protective role of GO solutions, however, disappeared at higher concentrations above complement-activating threshold. We discuss these results in relation to GO surface structure and properties, and implications for local administration and development of GO-based implantable devices.
authors.affiliation: Nanomedicine Laboratory, Centre for Pharmaceutical Nanotechnology and Nanotoxicology, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen Ø, Denmark.
authors.forename: Peter P
authors.initials: PP
authors.lastname: Wibroe
authors.affiliation: Nano-Science Center & Department of Chemistry, University of Copenhagen, DK-2100 Copenhagen Ø, Denmark.
authors.forename: Søren V
authors.initials: SV
authors.lastname: Petersen
authors.affiliation: Nano-Science Center & Department of Chemistry, University of Copenhagen, DK-2100 Copenhagen Ø, Denmark.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bovet
authors.affiliation: Nano-Science Center & Department of Chemistry, University of Copenhagen, DK-2100 Copenhagen Ø, Denmark.
authors.forename: Bo W
authors.initials: BW
authors.lastname: Laursen
authors.affiliation: Nanomedicine Laboratory, Centre for Pharmaceutical Nanotechnology and Nanotoxicology, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen Ø, Denmark. Electronic address: moein.moghimi@gmail.com.
authors.forename: S Moein
authors.initials: SM
authors.lastname: Moghimi
mesh_terms: D003167:Complement Activation; D003165:Complement System Proteins / Q000737:chemistry*; D006108:Graphite / Q000737:chemistry*; D006801:Humans; D018625:Microscopy, Atomic Force; D010084:Oxidation-Reduction; D010087:Oxides / Q000737:chemistry; D056951:Photoelectron Spectroscopy; D012995:Solubility; D013499:Surface Properties
chemical_list: D010087:Oxides; D006108:Graphite; D003165:Complement System Proteins
keywords: C5a; Complement system; Graphene oxide; Hemolysis; Innate immunity; Interleukin-6