The role of surface chemistry in the cytotoxicity profile of graphene.
Graphene and its derivative, because of their unique physical, electrical and chemical properties, are an important class of nanomaterials being proposed as foundational materials in nanomedicine as well as for a variety of industrial applications. A major limitation for graphene, when used in biomedical applications, is its poor solubility due to its rather hydrophobic nature. Therefore, chemical functionalities are commonly introduced to alter both its surface chemistry and biochemical activity. Here, we show that surface chemistry plays a major role in the toxicological profile of the graphene structures. To demonstrate this, we chemically increased the oxidation level of the pristine graphene and compared the corresponding toxicological effects along with those for the graphene oxide. X-ray photoelectron spectroscopy revealed that pristine graphene had the lowest amount of surface oxygen, while graphene oxide had the highest at 2.5% and 31%, respectively. Low and high oxygen functionalized graphene samples were found to have 6.6% and 24% surface oxygen, respectively. Our results showed a dose-dependent trend in the cytotoxicity profile, where pristine graphene was the most cytotoxic, with decreasing toxicity observed with increasing oxygen content. Increased surface oxygen also played a role in nanomaterial dispersion in water or cell culture medium over longer periods. It is likely that higher dispersity might result in graphene entering into cells as individual flakes ~1 nm thick rather than as more cytotoxic aggregates. In conclusion, changes in graphene's surface chemistry resulted in altered solubility and toxicity, suggesting that a generalized toxicity profile would be rather misleading. Copyright © 2016 John Wiley & Sons, Ltd.
Center of Integrative Nanotechnology Sciences, University of Arkansas at Little Rock, AR, 72204, USA.|Division of Neurotoxicology, National Center for Toxicological Research, Jefferson, AR, 72079, USA.
Waqar
W
Majeed
Center of Integrative Nanotechnology Sciences, University of Arkansas at Little Rock, AR, 72204, USA.
Shawn
S
Bourdo
Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, Jefferson, AR, 72079, USA.
Dayton M
DM
Petibone
Center of Integrative Nanotechnology Sciences, University of Arkansas at Little Rock, AR, 72204, USA.
Viney
V
Saini
Center of Integrative Nanotechnology Sciences, University of Arkansas at Little Rock, AR, 72204, USA.
Kieng Bao
KB
Vang
Center of Integrative Nanotechnology Sciences, University of Arkansas at Little Rock, AR, 72204, USA.
Zeid A
ZA
Nima
Center of Integrative Nanotechnology Sciences, University of Arkansas at Little Rock, AR, 72204, USA.
Karrer M
KM
Alghazali
Center of Integrative Nanotechnology Sciences, University of Arkansas at Little Rock, AR, 72204, USA.
Emilie
E
Darrigues
Center of Integrative Nanotechnology Sciences, University of Arkansas at Little Rock, AR, 72204, USA.|Department of Chemistry, University of Arkansas at Little Rock, AR, 72204, USA.
Anindya
A
Ghosh
Center of Integrative Nanotechnology Sciences, University of Arkansas at Little Rock, AR, 72204, USA.
Fumiya
F
Watanabe
Center of Integrative Nanotechnology Sciences, University of Arkansas at Little Rock, AR, 72204, USA.
Daniel
D
Casciano
Division of Neurotoxicology, National Center for Toxicological Research, Jefferson, AR, 72079, USA.
Syed F
SF
Ali
Center of Integrative Nanotechnology Sciences, University of Arkansas at Little Rock, AR, 72204, USA.
Alexandru S
AS
Biris
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D006108:Graphite / Q000737:chemistry* / Q000633:toxicity*; D006801:Humans; D049329:Nanostructures / Q000737:chemistry* / Q000633:toxicity*; D010100:Oxygen / Q000737:chemistry; D016716:PC12 Cells; D056951:Photoelectron Spectroscopy; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman; D013329:Structure-Activity Relationship; D013499:Surface Properties
D003470:Culture Media; D017382:Reactive Oxygen Species; D006108:Graphite; D010100:Oxygen
Graphene; PC12; TEM; WST-1; XPS