Biomedical Engineering Reference
In-Depth Information
(PEG) surfactant (compound
1
in Fig. 3.3), whereas in another case, oxidised
SWCNTs were covalently linked to PEG, through amidation of the carboxylic
moieties (compound
2
).
18
The authors suggest π-π stacking, together with
hydrophobic interactions, as binding forces between doxorubicin and
nanotubes. Moreover, they report a pH-dependent interaction: the loading
was performed at pH 9, the condition at which DOXO is deprotonated and
has low water solubility, reaching a doxorubicin-to-nanotube weight ratio of
~4:1; a decrease in the pH led to the release of the drug from the SWCNT
carrier, because of the consequent higher hydrophilicity of the protonated
drug. This mechanism can be very interesting in cancer therapy because of
the acidic environment of extracellular tissues in tumours, potentially leading
to selective drug release
in vivo
. The
in vitro
cytotoxicity of
1
was tested on
human glioblastoma cancer cells. The derivative induced cell death similar to
free DOXO at 10 μM concentration, even if the observed IC
50
value was higher
(~8 μM for
1
, ~2 μM for free DOXO).
O
O
n
O
N
H
O
O
O
O
OH
H
O
OH
O
O
OH
O
n
O
OH
OH
OH
N
OH
OH
OH
O
O
O
n
O
O
OH
O
O
O
OH
O
O
O
OH
O
O
O
O
NH
2
NH
2
NH
2
HO
= phospholipid-PEG
HO
HO
= phospholipid-PEG-RGD
3
1
2
Figure 3.3
Structures of compounds
1
-
3
. See also Colour Insert.
Furthermore, a targeted doxorubicin delivery was tested using a cyclic
arginine-glycine-aspartic acid (RGD) peptide, which acts as recognition
moiety for integrin α
V
β
3
receptors, overexpressed in a wide range of solid
tumours. The targeting agent was bound to the terminal group on the PEG
chain of the non-covalently functionalised SWCNT derivative, and then
doxorubicin was loaded (compound
3
). This conjugate, tested on integrin
α
V
β
3
-positive cells, showed enhanced drug delivery compared with the
derivative without RGD as conirmed by the IC
50
value, which was smaller for
3
(~3 μM) than for
1
.
Methotrexate is another well-known anticancer drug, but it has low
bioavailability and toxic side effects. Preliminary studies of CNT-based drug
delivery with this compound were performed by Pastorin
et al
.
19
The authors
covalently functionalised CNTs with methotrexate and tested the obtained
derivatives on human Jurkat T lymphocytes, inding a rapid internalisation
of compound
4
(Fig. 3.4)
and thereby proving the effectiveness of CNTs as
nanocarriers.
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