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respect to the drug itself. In fact there was a decrease in protein absorption,
which is responsible for an accelerated uptake by macrophages and 2 hours
after injection a much higher PTX presence was found in the intestine and the
reticuloendothelial system of different organs, such as the liver and spleen.
This is predictable behaviour for nanomaterials in general and can raise
concerns about toxicity for these organs. Nevertheless, the authors reported
a difference between the biodistribution of SWCNTs and and of PTX after
treatment with compound
7
, indicating a rapid release of the drug from the
conjugate in the various organs and tissues, probably because ester cleavage
by esterases. As a consequence, the drug seemed to be rapidly excreted,
lowering its toxicity. Importantly, 2 hours after injection, the PTX levels in
tumour were 10 times higher for derivative
7
than for taxol, and the tumor-
to-normal organ/tissue PTX uptake ratio was also higher, thus indicating a
better selectivity for the CNT-delivered drug.
O
O
O
O
O
O
N
H
O
H
O
O
O
O
OH
O
O
O
O
O
O
S
S
HN
O
OCH
3
N
O
NH
O
7
O
8
H
N
O
NH
HN
H
O
O
H
OH
O
NH
O
= PTX =
H
O
S
H
OH
O
OH
O
O
= phospholipid-PEG-PTX
Figure 3.5
Structures of compounds
7
and
8
.
A very interesting work recently published presents another study on
taxanes, using compound
8
as an anticancer drug delivery system targeted
by biotin towards cancer cells.
23
This construct is a prodrug, targeted by its biotin unit to cancer cells
overexpressing biotin receptors on their surface. Using a control SWCNT
derivative without biotin, the authors observed a temperature-dependent but
energy-independent internalisation. This is coherent with a non-endocytosis
mechanism, in accordance with the hypothesis of needle-like penetration of
CNTs through cell membranes. On the other hand, for the biotin conjugate,
the mechanism observed was endocytosis, and the degree of internalisation
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