title: Amine-modified graphene: thrombo-protective safer alternative to graphene oxide for biomedical applications.
abstract: Graphene and its derivatives have attracted significant research interest based on their application potential in different fields including biomedicine. However, recent reports from our laboratory and elsewhere have pointed to serious toxic effects of this nanomaterial on cells and organisms. Graphene oxide (GO) was found to be highly thrombogenic in mouse and evoked strong aggregatory response in human platelets. As platelets play a central role in hemostasis and thrombus formation, thrombotoxicity of GO potentially limits its biomedical applications. Surface chemistry of nanomaterials is a critical determinant of biocompatibility, and thus differentially functionalized nanomaterials exhibit varied cellular toxicity. Amine-modified carbon nanotubes have recently been shown to possess cytoprotective action, which was not exhibited by their relatively toxic carboxylated counterparts. We, therefore, evaluated the effect of amine modification of graphene on platelet reactivity. Remarkably, our results revealed for the first time that amine-modified graphene (G-NH(2)) had absolutely no stimulatory effect on human platelets nor did it induce pulmonary thromboembolism in mice following intravenous administration. Further, it did not evoke lysis of erythrocytes, another major cellular component in blood. These findings contrasted strikingly the observations with GO and reduced GO (RGO). We conclude that G-NH(2) is not endowed with thrombotoxic property unlike other commonly investigated graphene derivatives and is thus potentially safe for in vivo biomedical applications.
authors.affiliation: Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Singh
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Singh
authors.forename: Paresh P
authors.initials: PP
authors.lastname: Kulkarni
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Sonkar
authors.forename: José J A
authors.initials: JJ
authors.lastname: Grácio
authors.forename: Debabrata
authors.initials: D
authors.lastname: Dash
mesh_terms: D000588:Amines / Q000737:chemistry*; D001672:Biocompatible Materials / Q000009:adverse effects* / Q000737:chemistry / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D004337:Drug Carriers / Q000009:adverse effects* / Q000737:chemistry / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000187:drug effects; D006108:Graphite / Q000009:adverse effects* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D057054:Molecular Imaging; D010087:Oxides / Q000737:chemistry*; D012449:Safety; D013927:Thrombosis / Q000139:chemically induced*
chemical_list: D000588:Amines; D001672:Biocompatible Materials; D004337:Drug Carriers; D010087:Oxides; D006108:Graphite