Biomedical Engineering Reference
In-Depth Information
Yang
et al.
reported the preparation of a folate-targeted DNA transporter
with CNTs that is in principle exploitable to deliver siRNA to cancer cells.
20
They covalently functionalised SWCNTs with an aliphatic chain bearing a
positive charge and able to form electrostatic interactions with nucleic acids.
Then they bound luorescently labelled double-stranded DNA (dsDNA) to
this derivative and proved by UV a signiicant enhancement of the loading of
dsDNA for the positively charged SWCNTs (compound
5
) compared with the
uncharged SWCNTs. They further functionalised the derivative by wrapping
folic acid-modiied phospholipids (compound
6
). The complexes were tested
on mouse ovarian epithelial cells, showing an increased uptake for compound
6
, compared with
5
. Furthermore, the luorescently labelled dsDNA alone
was very poorly internalised, thus demonstrating the role of CNTs as carriers.
In a inal experiment with HeLa cells overexpressing folate receptors, the
internalisation of these derivatives was found to be much higher than in
normal HeLa cells, conirming the eficacy of the delivery system.
OH
N
N
NH
2
NH
2
N
N
N
O
O
NH
Glu
HN
O
CO
2
H
O
NH
HN
S
O
O
NH
3
NH
3
O
O
n
n
O
O
N
N
NH
NH
O
O
NH
3
NH
3
N
H
N
H
n
n
H
N
H
N
O
O
n
n
H
3
N
H
3
N
= Fluo-ds-DNA
= phospholipidic-PEG-Folic acid
4
5
6
Figure 3.4
Structures of compounds
4
-
6
.
Also taxanes, an important class of antineoplastic drugs, have been
conjugated with CNTs to prepare new drug delivery systems. Paclitaxel
(PTX) was linked to PEGylated SWCNTs (compound
7
in
Fig. 3.5)
and
then administered by intravenous injection to xenograft tumour mice
(PTX-resistant 4T1 murine breast cancer mice model) to test the
in vivo
eficacy of this compound.
21
The results were very promising, showing a
tumour growth inhibition of almost 60% for compound
7
, while only 28%
and 21% of inhibition was obtained by taxol and PEG-PTX, respectively. A
higher apoptosis level and a diminished proliferation of active cells were
observed in the presence of the CNT derivative, when compared with the
drug itself. It is important to notice that the PEGylated CNT complex did not
demonstrate toxicity in mice, as reported in another paper by Liu
et al.
22
In
the pharmacokinetic studies, compound
7
showed an increased plasmatic
half-life, coherently with the enhanced hydrophilicity of the conjugate with
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