Synthesis and Physicochemical Transformations of Size-Sorted Graphene Oxide during Simulated Digestion and Its Toxicological Assessment against an In Vitro Model of the Human Intestinal Epithelium
Dimitrios Bitounis
Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, T.H. Chan School of Public Health, Harvard University, 655 Huntington Ave, Boston, MA, 02115 USA
Search for more papers by this authorDorsa Parviz
Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue 66-570b, Cambridge, MA, 02139 USA
Search for more papers by this authorXiaoqiong Cao
Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, T.H. Chan School of Public Health, Harvard University, 655 Huntington Ave, Boston, MA, 02115 USA
Search for more papers by this authorCarlo A. Amadei
John A. Paulson School of Engineering and Applied Sciences, Harvard University, 29 Oxford St, Cambridge, MA, 02138 USA
Search for more papers by this authorChad D. Vecitis
John A. Paulson School of Engineering and Applied Sciences, Harvard University, 29 Oxford St, Cambridge, MA, 02138 USA
Search for more papers by this authorElsie M. Sunderland
John A. Paulson School of Engineering and Applied Sciences, Harvard University, 29 Oxford St, Cambridge, MA, 02138 USA
Search for more papers by this authorBrian D. Thrall
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, 99354 USA
Search for more papers by this authorMingliang Fang
School of Civil and Environmental Engineering, Nanyang Technological University, Singapore, 639798 Singapore
Search for more papers by this authorCorresponding Author
Michael S. Strano
Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue 66-570b, Cambridge, MA, 02139 USA
E-mail: [email protected], [email protected]
Search for more papers by this authorCorresponding Author
Philip Demokritou
Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, T.H. Chan School of Public Health, Harvard University, 655 Huntington Ave, Boston, MA, 02115 USA
E-mail: [email protected], [email protected]
Search for more papers by this authorDimitrios Bitounis
Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, T.H. Chan School of Public Health, Harvard University, 655 Huntington Ave, Boston, MA, 02115 USA
Search for more papers by this authorDorsa Parviz
Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue 66-570b, Cambridge, MA, 02139 USA
Search for more papers by this authorXiaoqiong Cao
Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, T.H. Chan School of Public Health, Harvard University, 655 Huntington Ave, Boston, MA, 02115 USA
Search for more papers by this authorCarlo A. Amadei
John A. Paulson School of Engineering and Applied Sciences, Harvard University, 29 Oxford St, Cambridge, MA, 02138 USA
Search for more papers by this authorChad D. Vecitis
John A. Paulson School of Engineering and Applied Sciences, Harvard University, 29 Oxford St, Cambridge, MA, 02138 USA
Search for more papers by this authorElsie M. Sunderland
John A. Paulson School of Engineering and Applied Sciences, Harvard University, 29 Oxford St, Cambridge, MA, 02138 USA
Search for more papers by this authorBrian D. Thrall
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, 99354 USA
Search for more papers by this authorMingliang Fang
School of Civil and Environmental Engineering, Nanyang Technological University, Singapore, 639798 Singapore
Search for more papers by this authorCorresponding Author
Michael S. Strano
Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue 66-570b, Cambridge, MA, 02139 USA
E-mail: [email protected], [email protected]
Search for more papers by this authorCorresponding Author
Philip Demokritou
Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, T.H. Chan School of Public Health, Harvard University, 655 Huntington Ave, Boston, MA, 02115 USA
E-mail: [email protected], [email protected]
Search for more papers by this authorAbstract
In the last decade, along with the increasing use of graphene oxide (GO) in various applications, there is also considerable interest in understanding its effects on human health. Only a few experimental approaches can simulate common routes of exposure, such as ingestion, due to the inherent complexity of the digestive tract. This study presents the synthesis of size-sorted GO of sub-micrometer- or micrometer-sized lateral dimensions, its physicochemical transformations across mouth, gastric, and small intestinal simulated digestions, and its toxicological assessment against a physiologically relevant, in vitro cellular model of the human intestinal epithelium. Results from real-time characterization of the simulated digestas of the gastrointestinal tract using multi-angle laser diffraction and field-emission scanning electron microscopy show that GO agglomerates in the gastric and small intestinal phase. Extensive morphological changes, such as folding, are also observed on GO following simulated digestion. Furthermore, X-ray photoelectron spectroscopy reveals that GO presents covalently bound N-containing groups on its surface. It is shown that the GO employed in this study undergoes reduction. Toxicological assessment of the GO small intestinal digesta over 24 h does not point to acute cytotoxicity, and examination of the intestinal epithelium under electron microscopy does not reveal histological alterations. Both sub-micrometer- and micrometer-sized GO variants elicit a 20% statistically significant increase in reactive oxygen species generation compared to the untreated control after a 6 h exposure.
Conflict of Interest
The authors declare no conflict of interest.
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