Chemistry Reference
In-Depth Information
weighted images. Various
studies showed that
they can be applied as probes for multimodal imaging. Indeed the
internalization of these particles can be monitored both by FI and
MRI. It was demonstrated that silica-coated QD do not alter the
viability of labeled cells. Furthermore, labeled cells under continuous
UV or laser irradiation remain viable, whereas a cytotoxic effect
is generated when cells are loaded with uncoated QD. The silica
shell seems to suppress the photosensitization effect, which was
previously reported for uncoated QD. The low toxicity of these
contrast agents is encouraging for
in vitro
and
in vivo
applications. However, the
accumulation in spleen must be solved since this reflects the uptake
by macrophages, which is commonly observed when positively
charged particles are intravenously injected. This capture should be
overcome by PEGylation.
The encapsulation of TOP/TOPO-coated QD by silica shell was
also performed via reverse microemulsion technique [54]. In this
case, the silica shell was formed between the QD and the TOP/
TOPO layer. The post-functionalization of the resulting particles
for rendering them paramagnetic and hydrophilic was realized
according to the protocol developed by Mulder's research group for
TOP/TOPO-coated QD [57].
Hydrophobic TOP/TOPO-coated QD can be rendered hydrophilic
by coating them with amphiphilic PEGylated phospholipids
(PEG-lipids: PEG-DSPE (1,2-distearoyl-sn-glycero-3-phosphoeth-
anolamine-
in vivo
[methoxy-(poly(ethylene glycol))-2000]). These
molecules are widely used to stabilize liposomes for pharmaceuti-
cal applications because PEG chains form a hydrophilic layer on the
liposomal surface. The coating of hydrophobic QD (or QD encapsu-
lated in silica shell) with a mixture of PEG-lipids and of paramag-
netic lipids (i.e., gadolinium (III) chelate conjugated to hydrophobic
stearylamide) yields water soluble and fluorescent positive contrast
agents for FI and MRI. The post-functionalization of hydrophobic
silica-coated QD with PEG-lipids improves markedly the biodistri-
bution and the pharmacokinetics of these contrast agents [58].
Moreover, some PEG-lipids, which are terminated by maleimide
moiety, allow for bioconjugation. Mulder's group succeeded in
functionalizing these nanoprobes by RGD and annexin A5 proteins
[55, 56]. The grafting of RGD, which is well known for targeting
N-
α
β
v
5
α
β
and
integrins, favors the uptake of these paramagnetic QD by
HUVEC due to the over-expression of
v
3
α
β
integrins. The ability of
v
3
