is very representative, which can be readily applicable in other carbon nanomaterials. Functionalized nano-graphene derivatives have attracted continuous attention
in biomedical applications [70]. Generally, graphene derivatives have two primary
chemical components—graphene oxide (GO) and reduced graphene oxide (rGO).
To conduct surface modification with more biocompatible polymers (mostly PEG),
GO can react with amine-containing molecules due to the abundant oxygencontaining groups (e.g. carboxyl, hydroxyl, or ketone moieties) on surface [70]. In a
recent study, the investigators indicated that PAA functionalization of graphene
oxide may be superior to PEGylation in terms of biocompatibility in vivo [71]. On
the other hand, rGO derivatives possess much scarce oxygen-containing groups, the
surface engineering is usually achieved via p–p interactions with their aromatic
structure.
Surface modification of graphene-based nanomaterials has been thoroughly
discussed in a recent review article [72]. Amine-containing branched PEG molecules can be a frequent option for GO surface decoration. Post this modification,
various radiometals (e.g.
64 Cu or
66 Ga)—labeled nano-GO was used for targeting of
both primary and metastatic breast tumors in murine models [73–75]. In an early
study, trastuzumab (against HER2 receptor) was directly conjugated onto nano-GO
via amide bonding without PEGylation, and benzyl- diethylenetriaminepentaacetic
acid (BnDTPA) was loaded onto GO via p–p stacking for further labeling with
111 In [76]. A surprisingly high uptake was achieved in HER-2 positive tumor
(*15% injection dose per gram, %ID/g at 72 h post-injection with a
tumor-to-muscle of 7:1) from this study, and despite that the liver uptake was high,
the accumulation of
111 In-GO-trastuzumab in spleen was not high, proving that
direct surface engineering of GO with biomolecules like antibodies was also
acceptable for their in vivo applications. On the other hand, C 18 PMH-PEG is one of
the star molecules for rGO surface functionalization. Very recently, rGO was
proved to possess strong interaction with
64 Cu via metal-p electron interactions, and
this chelator-free labeled
64
Cu-rGO-PEG was confirmed to have good stability
in vivo along with tumor-homing properties (Fig. 10.3b) [77], while
64 Cu was
previously labeled onto NOTA molecules attached on C 18 PMH-PEG [78]. In some
situation, when rGO was complexed with other nanomaterials, e.g. iron oxide
nanoparticles, covalent PEGylation could be achieved onto the surface of ‘loaded’
nanomaterials [79].
10.3.1.3 Metal-Based Nanomaterials
Metal-based or metal-containing nanomaterials represents one of the largest family
within the inorganic nanomaterials, and representative examples include (but not
limited to) noble metal-based (e.g. gold) nanomaterials [80], quantum dots [81],
upconversion nanoparticles (UCNPs) [82], zinc oxide (ZnO) nanomaterials [83],
among many others. Judging from their metal contents, the initial step for metal
nanomaterial surface engineering is to use metal-coordinating molecules for interactions. One good example is that thiol-containing molecules (e.g. glutathione) are
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in biomedical applications [70]. Generally, graphene derivatives have two primary
chemical components—graphene oxide (GO) and reduced graphene oxide (rGO).
To conduct surface modification with more biocompatible polymers (mostly PEG),
GO can react with amine-containing molecules due to the abundant oxygencontaining groups (e.g. carboxyl, hydroxyl, or ketone moieties) on surface [70]. In a
recent study, the investigators indicated that PAA functionalization of graphene
oxide may be superior to PEGylation in terms of biocompatibility in vivo [71]. On
the other hand, rGO derivatives possess much scarce oxygen-containing groups, the
surface engineering is usually achieved via p–p interactions with their aromatic
structure.
Surface modification of graphene-based nanomaterials has been thoroughly
discussed in a recent review article [72]. Amine-containing branched PEG molecules can be a frequent option for GO surface decoration. Post this modification,
various radiometals (e.g.
64 Cu or
66 Ga)—labeled nano-GO was used for targeting of
both primary and metastatic breast tumors in murine models [73–75]. In an early
study, trastuzumab (against HER2 receptor) was directly conjugated onto nano-GO
via amide bonding without PEGylation, and benzyl- diethylenetriaminepentaacetic
acid (BnDTPA) was loaded onto GO via p–p stacking for further labeling with
111 In [76]. A surprisingly high uptake was achieved in HER-2 positive tumor
(*15% injection dose per gram, %ID/g at 72 h post-injection with a
tumor-to-muscle of 7:1) from this study, and despite that the liver uptake was high,
the accumulation of
111 In-GO-trastuzumab in spleen was not high, proving that
direct surface engineering of GO with biomolecules like antibodies was also
acceptable for their in vivo applications. On the other hand, C 18 PMH-PEG is one of
the star molecules for rGO surface functionalization. Very recently, rGO was
proved to possess strong interaction with
64 Cu via metal-p electron interactions, and
this chelator-free labeled
64
Cu-rGO-PEG was confirmed to have good stability
in vivo along with tumor-homing properties (Fig. 10.3b) [77], while
64 Cu was
previously labeled onto NOTA molecules attached on C 18 PMH-PEG [78]. In some
situation, when rGO was complexed with other nanomaterials, e.g. iron oxide
nanoparticles, covalent PEGylation could be achieved onto the surface of ‘loaded’
nanomaterials [79].
10.3.1.3 Metal-Based Nanomaterials
Metal-based or metal-containing nanomaterials represents one of the largest family
within the inorganic nanomaterials, and representative examples include (but not
limited to) noble metal-based (e.g. gold) nanomaterials [80], quantum dots [81],
upconversion nanoparticles (UCNPs) [82], zinc oxide (ZnO) nanomaterials [83],
among many others. Judging from their metal contents, the initial step for metal
nanomaterial surface engineering is to use metal-coordinating molecules for interactions. One good example is that thiol-containing molecules (e.g. glutathione) are
194
D. Chen and H. Hong