Chemistry Reference
In-Depth Information
K7RGD sequence and negatively charged PSS layer. RGD sequence
is well known for its strong interaction with
α
β
integrin that are
upregulated in growing endothelial and angiogenic cancer cells.
Such a functionalization led to the efficient targeting of human colon
cancer (HT-29) cells and calf pulmonary artery endothelial (CPAE)
cells as revealed by
v
3
experiments monitored by FI and MRI.
Although these results are very promising, the
in vitro
in vivo
application of
these contrast agents is not yet validated.
The silylated gadolinium chelates can also be successfully applied
for the functionalization of metal oxide nanoparticles since they
are covered by -OH groups, which act as anchoring sites. Frias
et
al.
reported the modification of boehmite (AlO(OH)) nanoparticles
with silylated gadolinium (III) chelates (derivatives of DO3A) [25].
These particles are, therefore, able to enhance the positive contrast
of magnetic resonance images. As expected, these ligands, which
are covalently bound to the nanoparticle surface through the
condensation between methoxy groups of silylated ligands and -OH
groups of the surface, are able to capture luminescent lanthanide
ions (Eu
3+
3+
).
The post-functionalization of fluorescent silica nanoparticles
by silylated gadolinium (III) chelates is very efficient, as
demonstrated by the studies of Lin's research group. Since most
of the clinically approved gadolinium (III) chelates are based on
polyaminocarboxylate motif, they can be easily immobilized on
aminated nanoparticles through the formation of amide linkage
(Schemes 4.4 and 4.5). Amine functions in nanoparticles are
generally introduced by the inorganic copolymerization of TEOS
and aminated polysiloxane precursors (APP like ATPES, APTMS)
or by the derivatization of oxide nanoparticles by APP (Scheme
4.3). Delville
and Tb
succeeded in converting alumina and silica
nanoparticles into fluorescent and paramagnetic contrast agents
[26]. This was performed after the coating of the bare nanoparticles
with a polysiloxane shell yielded by the hydrolysis-condensation
of APTMS. Such an encapsulation allows tethering organic dyes
(rhodamine isothiocyanate) and polyaminocarboxylate ligand
(DTPA derivative) for the immobilization of gadolinium (III) ions
onto the surface of the nanoparticles. DTPA ligand was grafted to the
surface either by the reaction between aminated surface and bis-
anhydride derivative of DTPA or by the peptide reaction promoted
by the carbodiimide EDC in presence of NHS between aminated
et al.
