Chemistry Reference
In-Depth Information
organic acids or by the grafting of PEG-silane molecules. After their
synthesis in DEG, the resulting gadolinium oxide cores are coated
by DEG molecules, which can be replaced in hot DEG by citric acid
or dimercaptosuccinic acid [110, 111]. This layer of organic acid
molecules acts as a primer for further functionalization and, in
peculiar, for PEGylation, which is required for biological applications.
The grafting of nonimmunogenic and nonantigenic PEG is expected
to render the gadolinium oxide cores more robust, to improve the
colloidal stability in biological media, to favor uptake by cells and
enhance blood retention. Citric acid-coated gadolinium oxide cores
were derivatized by PEG chains ended by a thiol (SH) group and
an amino (NH
@CA-PEG). The amino group of PEG
permits the condensation with carboxylic acid groups of citric acid,
which were activated by EDC/NHS mixture prior to the coupling
reaction. Thiol groups at the opposite extremity can be used for the
grafting of molecules bearing maleimide group [112]. Since each
dimercaptosuccinimide (DMSA) molecule grafted to gadolinium
oxide cores carries two thiol functions, Mal-PEG-NHS (Mal and NHS
for maleimide and
) group (Gd
O
2
2
3
hydroxysuccinimide groups, respectively)
was used for the PEGylation of DMSA-capped gadolinium oxide
cores. The covalent coupling of PEG is ensured by the formation of
thioether linkage resulting from the condensation of the thiol group
of DMSA with maleimide moiety of Mal-PEG-NHS (Gd
N-
@DMSA-
PEG) [112]. The presence of NHS group affords the possibility of
grafting aminated molecules (typically biomolecules, which are rich
in amine functions) onto the PEGylated nanoparticles [112]. The
PEGylation can also be performed using PEG-silane since alkoxysilyl
end-group of PEG-silane favors its grafting on oxide nanoparticles
through the condensation between the alkoxysilyl groups and
hydroxyl (OH) groups present on the surface of the oxide materials
(Gd
O
2
3
@PEG) [113]. These PEGylated oxide nanoparticles, which
are prepared by the research group of Linköping University, exhibit,
as expected, relatively high longitudinal relaxivity
O
2
3
r
. The relaxivity
1
values of Gd
@CA-PEG
(based on the amount of gadolinium (III) ions in each sample)
were 12.0, 14.2, and 7.8 mM
O
@PEG, Gd
O
@DMSA-PEG, and Gd
O
2
3
2
3
2
3
−1
−1
s
, respectively [114]. Except for
Gd
@CA-PEG, these PEGylated gadolinium oxide nanoparticles
exhibit a higher relaxivity than the one of GadoSiPEG developed by
Tillement's research group (see above). The longitudinal relaxivities
of GadoSiPEG nanoparticles containing the smallest gadolinium
O
2
3
