can be decent candidates for chelating or burying the metal ions to decrease
potential toxicity.
In 2013, Kanakia et al. reported the use of dextran-coated graphene nanoplatelets
(GNP–Dex) with Mn
2+ ions as enhanced T 1 -weighted MRI contrast agents [70].
The preparation of such complex was simply achieved by intercalating Mn
2+ ions in
GNP–Dex, which was stable in the physiological conditions. Remarkably, the r 1
relaxivity of GNP–Dex–Mn
2+ system was 92 mM
−1 s
−1 (per Mn
2+ ion), which
greatly exceeds that of clinical Mn
2+ -based contrast agents. In addition, the T 1 -
weighted phantom imaging also showed marked contrast enhancement.
In 2014, Gizzatov et al. employed functionalized graphene nanoribbons (GNRs)
to coordinate Gd
3+ ion [71]. Highly carboxyphenylated GNRs were produced by
reductively cutting multi-walled carbon nanotubes (MWCNTs) using K/Na alloy,
which were subsequently functionalized with p-carboxyphenyldiazonium to yield
carboxyphenyl GNRs (average width 125–280 nm, average thickness 7–15 nm).
Obtained GNRs were successfully coordinated with Gd
3+ ions to form Gd–GNRs
complex without additional surfactants. Notably, Gd–GNRs composite significantly
enhanced the relaxation rates of T1 and T2 (spin-spin relaxation) at 1.41 T, by
displaying r 1 and r 2 values of 70 ± 6 and 108 ± 9 Mm
−1 s
−1 respectively. The T 1 -
and T 2 -weighted phantom images further confirmed that the use of Gd–GNRs
composite results in better MRI contrasts, which greatly exceeds those of GNRs or
H 2 O-based images.
4.5.2 Paramagnetic Nanoparticles-Decorated Graphene
Currently, most of the commercial nanoparticle-based MRI contrast agents utilize
magnetic iron oxides (i.e. superparamagnetic iron oxide—SPIO) [72]. In general,
the mechanism of relaxation of superparamagnetic agents is different from that for
paramagnetic ion-based agents. Paramagnetic nanoparticles’ large magnetic field
leads to water molecule spin dephasing around the nanoparticle, producing transverse relaxation T 2 contrast. As graphene derivatives can be used as a template for
the growth of nanoparticles or efficiently conjugated with capped ligands, graphene
derivatives-paramagnetic nanoparticles can be easily prepared as T 2 contrastenhancing agents [73].
In 2011, Chen et al. reported the first attempt to employ graphene-based
nanomaterial as a novel T 2 contrast agent [74]. In the study, Fe 3 O 4 –GOs composite
was prepared by coating Fe 3 O 4 nanoparticles with dimercaptosuccinic acid
(DMSA), which were subsequently conjugated with aminodextran (AMD). Finally,
Fe 3 O 4 –DMSA–AMD and GOs were covalently grafted by EDC coupling, which
yielded the final composite with an average size of 174.4 nm. Remarkably, the T 2
relaxation rate of Fe 3 O 4 –GOs (per Fe concentration) was significantly enhanced by
exhibiting r 2 = 76 Mm
−1 s
−1 , which greatly exceeded those of other composites
without GOs; 24 and 21 Mm
−1 s
−1 , respectively for DMSA–Fe 3 O 4 and
AMD–Fe 3 O 4 .
4 Graphene-Based Nanomaterials
93
potential toxicity.
In 2013, Kanakia et al. reported the use of dextran-coated graphene nanoplatelets
(GNP–Dex) with Mn
2+ ions as enhanced T 1 -weighted MRI contrast agents [70].
The preparation of such complex was simply achieved by intercalating Mn
2+ ions in
GNP–Dex, which was stable in the physiological conditions. Remarkably, the r 1
relaxivity of GNP–Dex–Mn
2+ system was 92 mM
−1 s
−1 (per Mn
2+ ion), which
greatly exceeds that of clinical Mn
2+ -based contrast agents. In addition, the T 1 -
weighted phantom imaging also showed marked contrast enhancement.
In 2014, Gizzatov et al. employed functionalized graphene nanoribbons (GNRs)
to coordinate Gd
3+ ion [71]. Highly carboxyphenylated GNRs were produced by
reductively cutting multi-walled carbon nanotubes (MWCNTs) using K/Na alloy,
which were subsequently functionalized with p-carboxyphenyldiazonium to yield
carboxyphenyl GNRs (average width 125–280 nm, average thickness 7–15 nm).
Obtained GNRs were successfully coordinated with Gd
3+ ions to form Gd–GNRs
complex without additional surfactants. Notably, Gd–GNRs composite significantly
enhanced the relaxation rates of T1 and T2 (spin-spin relaxation) at 1.41 T, by
displaying r 1 and r 2 values of 70 ± 6 and 108 ± 9 Mm
−1 s
−1 respectively. The T 1 -
and T 2 -weighted phantom images further confirmed that the use of Gd–GNRs
composite results in better MRI contrasts, which greatly exceeds those of GNRs or
H 2 O-based images.
4.5.2 Paramagnetic Nanoparticles-Decorated Graphene
Currently, most of the commercial nanoparticle-based MRI contrast agents utilize
magnetic iron oxides (i.e. superparamagnetic iron oxide—SPIO) [72]. In general,
the mechanism of relaxation of superparamagnetic agents is different from that for
paramagnetic ion-based agents. Paramagnetic nanoparticles’ large magnetic field
leads to water molecule spin dephasing around the nanoparticle, producing transverse relaxation T 2 contrast. As graphene derivatives can be used as a template for
the growth of nanoparticles or efficiently conjugated with capped ligands, graphene
derivatives-paramagnetic nanoparticles can be easily prepared as T 2 contrastenhancing agents [73].
In 2011, Chen et al. reported the first attempt to employ graphene-based
nanomaterial as a novel T 2 contrast agent [74]. In the study, Fe 3 O 4 –GOs composite
was prepared by coating Fe 3 O 4 nanoparticles with dimercaptosuccinic acid
(DMSA), which were subsequently conjugated with aminodextran (AMD). Finally,
Fe 3 O 4 –DMSA–AMD and GOs were covalently grafted by EDC coupling, which
yielded the final composite with an average size of 174.4 nm. Remarkably, the T 2
relaxation rate of Fe 3 O 4 –GOs (per Fe concentration) was significantly enhanced by
exhibiting r 2 = 76 Mm
−1 s
−1 , which greatly exceeded those of other composites
without GOs; 24 and 21 Mm
−1 s
−1 , respectively for DMSA–Fe 3 O 4 and
AMD–Fe 3 O 4 .
4 Graphene-Based Nanomaterials
93