all these variants showed only negligible cytotoxicity. Sasidharan et al. reported the
importance of functional groups in attenuating potential toxicity induced by
graphene-based nanomaterials without any functional groups [31]. They suggested
that hydrophobic interactions between the basal planes of graphene-based nanomaterials with the cell membrane likely provoke toxicity including apoptosis triggered by elevated intracellular reactive oxygen species and the cell membrane
deformation. In the presence of functional groups, however, the hydrophobic
interactions can be hindered to some extent, thus preventing subsequent toxicity.
The presence of functional groups also plays a role in enzyme-catalyzed
biodegradation of large graphene-based nanomaterials, which will be highlighted
later in detail.
4.3.2 In Vivo Toxicity
For biomedical applications, in vivo toxicology and biodistribution of
graphene-based nanomaterials have been explored recently. In 2010, Yang et al.
studied the long-term in vivo biodistribution and pharmacokinetics of PEGylated
125 I-nanographene sheets with (NGS) [45]. With systemic toxicology examination,
the authors confirmed the radioactivity of NGS in the blood and various organs after
intravenous (i.v.) injection. Notably, radioactive NGS decreased persistently in
most organs, which were presumably excreted by fecal or renal routes. On hematology and blood biochemistry examination to investigate long-term in vivo effect,
NGS injection (20 mg/kg) did not show any significant damages in the mice until
3 months. In 2013, the same researchers carried out similar investigations with
functionalized nano-GOs through two other major administration routes:
intraperitoneal (i.p.) injection and oral uptake [30]. Interestingly, while oral feeding
did not induce any notable accumulation of nano-GOs in tissues, i.p. injected mice
exhibited highly accumulated nano-GOs in the mononuclear phagocytic (reticuloendothelial) system. Nevertheless, both did not induce any severe toxicity in
mice. More recently, Nurunnabi et al. carried out long-term in vivo toxicology and
biodistribution studies on mice treated with carboxylated GQDs through i.v.
injection [46]. The in vivo and ex vivo images showed that GQDs were distributed
mainly in the kidney, liver, spleen, lung, and tumor sites (Fig. 4.2). And these
accumulations did not elicit any organ lesions or damages, confirmed by further
analyses on mice administered with 5 or 10 mg/kg GQDs at 21 days. Although
some reports argue that high doses of large GOs can evoke severe damages in cells
[36], most studies have confirmed that nano-GOs and GQDs exhibit respectable
biocompatibility which can presumably be cleared out through kidneys without
significant accumulation.
86
J. M. Yoo et al.
importance of functional groups in attenuating potential toxicity induced by
graphene-based nanomaterials without any functional groups [31]. They suggested
that hydrophobic interactions between the basal planes of graphene-based nanomaterials with the cell membrane likely provoke toxicity including apoptosis triggered by elevated intracellular reactive oxygen species and the cell membrane
deformation. In the presence of functional groups, however, the hydrophobic
interactions can be hindered to some extent, thus preventing subsequent toxicity.
The presence of functional groups also plays a role in enzyme-catalyzed
biodegradation of large graphene-based nanomaterials, which will be highlighted
later in detail.
4.3.2 In Vivo Toxicity
For biomedical applications, in vivo toxicology and biodistribution of
graphene-based nanomaterials have been explored recently. In 2010, Yang et al.
studied the long-term in vivo biodistribution and pharmacokinetics of PEGylated
125 I-nanographene sheets with (NGS) [45]. With systemic toxicology examination,
the authors confirmed the radioactivity of NGS in the blood and various organs after
intravenous (i.v.) injection. Notably, radioactive NGS decreased persistently in
most organs, which were presumably excreted by fecal or renal routes. On hematology and blood biochemistry examination to investigate long-term in vivo effect,
NGS injection (20 mg/kg) did not show any significant damages in the mice until
3 months. In 2013, the same researchers carried out similar investigations with
functionalized nano-GOs through two other major administration routes:
intraperitoneal (i.p.) injection and oral uptake [30]. Interestingly, while oral feeding
did not induce any notable accumulation of nano-GOs in tissues, i.p. injected mice
exhibited highly accumulated nano-GOs in the mononuclear phagocytic (reticuloendothelial) system. Nevertheless, both did not induce any severe toxicity in
mice. More recently, Nurunnabi et al. carried out long-term in vivo toxicology and
biodistribution studies on mice treated with carboxylated GQDs through i.v.
injection [46]. The in vivo and ex vivo images showed that GQDs were distributed
mainly in the kidney, liver, spleen, lung, and tumor sites (Fig. 4.2). And these
accumulations did not elicit any organ lesions or damages, confirmed by further
analyses on mice administered with 5 or 10 mg/kg GQDs at 21 days. Although
some reports argue that high doses of large GOs can evoke severe damages in cells
[36], most studies have confirmed that nano-GOs and GQDs exhibit respectable
biocompatibility which can presumably be cleared out through kidneys without
significant accumulation.
86
J. M. Yoo et al.