4.3 Toxicity of Graphene-Based Nanomaterials
A number of different carbon allotropes including carbon nanotubes (CNTs),
fullerenes, and graphene-based nanomaterials have been considered in various
biomedical applications. Nevertheless, previous studies consistently reported toxicity entirely different according to the types of materials, allotropes, despite their
similarities in the chemical compositions. While CNTs exhibit relatively high levels
of toxicity in many studies, recent investigations showed that most graphene-based
materials show negligible toxicities [28, 29].
4.3.1 In Vitro Toxicity
Regarding GOs and GQDs applied in biomedicine, several groups recently investigated their in vitro toxicity and cellular uptake on different cell types. The studies
generally agreed on the lack of significance toxicity despite internalization in the
cells, which make graphene-based nanomaterials candidates for diverse biological
studies [30–35]. On the contrary, studies suggested that certain forms of GOs and
GQDs can be damaging seriously to the cells [34, 35]. Micrometer-sized GOs were
found severely toxic on a number of different cell lines on a thorough cytotoxicity
screening study [36]. Large GOs and GO-based nanoplatelets induced significant
cytotoxicity and thereby could cause lung diseases [37, 38]. The toxicity of
graphene-based nanomaterials was believed to depend strongly on the particle size
and nano-sized GOs and GQDs was without significant toxicity [35, 38, 39].
Akhavan et al., however, proposed an entirely different mechanism of toxicity. The
authors suggested that the direct interaction between the edges of these
graphene-based nanomaterials and the cell membranes led to the cytotoxicity,
which was independent of the particle size and thus even nano-sized GOs and
GQDs could also induce lethal damages to cells [40, 41]. In addition, the toxicity
studies of other nanoparticles suggested that cellular internalization and cytotoxicity
also depended on the shape as well [42, 43]. To sum up, the mechanism of cytotoxicity of graphene-based nanomaterials still remains unclear and further studies
are warranted.
The effects of edge functionalization on cytotoxicity and membrane permeability
have also been investigated thoroughly. Edge modification with PEG and other
hydrophilic polymers have been the most widely employed technique to improve
biocompatibility in physiological conditions while reducing the cytotoxic effects
[7]. In 2014, Yuan et al. and Kong et al. modified GQDs with various functional
groups including PEG, NH 2 , COOH, and CO–N(CH 3 ) 2 and explored the effects on
their cytotoxicity and membrane permeability [33, 44]. Although their membrane
permeability differed among these GQDs variants by displaying 8, 13, and 19%
permeability respectively for GQDs with PEG, OH/COOH, and NH 2 groups,
4 Graphene-Based Nanomaterials
85
A number of different carbon allotropes including carbon nanotubes (CNTs),
fullerenes, and graphene-based nanomaterials have been considered in various
biomedical applications. Nevertheless, previous studies consistently reported toxicity entirely different according to the types of materials, allotropes, despite their
similarities in the chemical compositions. While CNTs exhibit relatively high levels
of toxicity in many studies, recent investigations showed that most graphene-based
materials show negligible toxicities [28, 29].
4.3.1 In Vitro Toxicity
Regarding GOs and GQDs applied in biomedicine, several groups recently investigated their in vitro toxicity and cellular uptake on different cell types. The studies
generally agreed on the lack of significance toxicity despite internalization in the
cells, which make graphene-based nanomaterials candidates for diverse biological
studies [30–35]. On the contrary, studies suggested that certain forms of GOs and
GQDs can be damaging seriously to the cells [34, 35]. Micrometer-sized GOs were
found severely toxic on a number of different cell lines on a thorough cytotoxicity
screening study [36]. Large GOs and GO-based nanoplatelets induced significant
cytotoxicity and thereby could cause lung diseases [37, 38]. The toxicity of
graphene-based nanomaterials was believed to depend strongly on the particle size
and nano-sized GOs and GQDs was without significant toxicity [35, 38, 39].
Akhavan et al., however, proposed an entirely different mechanism of toxicity. The
authors suggested that the direct interaction between the edges of these
graphene-based nanomaterials and the cell membranes led to the cytotoxicity,
which was independent of the particle size and thus even nano-sized GOs and
GQDs could also induce lethal damages to cells [40, 41]. In addition, the toxicity
studies of other nanoparticles suggested that cellular internalization and cytotoxicity
also depended on the shape as well [42, 43]. To sum up, the mechanism of cytotoxicity of graphene-based nanomaterials still remains unclear and further studies
are warranted.
The effects of edge functionalization on cytotoxicity and membrane permeability
have also been investigated thoroughly. Edge modification with PEG and other
hydrophilic polymers have been the most widely employed technique to improve
biocompatibility in physiological conditions while reducing the cytotoxic effects
[7]. In 2014, Yuan et al. and Kong et al. modified GQDs with various functional
groups including PEG, NH 2 , COOH, and CO–N(CH 3 ) 2 and explored the effects on
their cytotoxicity and membrane permeability [33, 44]. Although their membrane
permeability differed among these GQDs variants by displaying 8, 13, and 19%
permeability respectively for GQDs with PEG, OH/COOH, and NH 2 groups,
4 Graphene-Based Nanomaterials
85