Biomedical Engineering Reference
In-Depth Information
Moreover, nonspherical nanocarriers (e.g., CNTs) have been reported to be retained in the lymph
nodes for longer periods of time compared to spherical nanocarriers (e.g., liposomes)
[12]
. Thus,
CNTs might be used for targeting lymph node cancers as shown by Yang and coworkers
[13,14]
. In
these studies, magnetic nanoparticles containing the anticancer drug cisplatin were entrapped into
FA-functionalized MWNTs. An external magnet was employed to drag the nanotubes to the lymph
nodes where the drug was shown to be released over several days and the tumor to be selectively
inhibited.
Dhar and coworkers
[15]
have developed what they called the “longboat delivery system” (
Figure
20.4
). A complex of cisplatin and FA derivative was attached to a functionalized SWNT via a number
of amide bonds to comprise the “longboat” which has been reported to be taken up by cancer cells
via endocytosis, followed by the release of the drug and its subsequent interaction with the nuclear
DNA. Another platinum anticancer drug, namely carboplatin, after been filled into CNTs has shown
to inhibit the proliferation of urinary bladder cancer cells
in vitro
. In another study, the anticancer
effect has been shown to be dependent on the method used to entrap the drug in the CNTs, which
highlighted the possible effects of preparation conditions on the therapeutic activity of therapeutic
molecules associated with CNTs
[16]
.
Paclitaxel is a poorly water-soluble anticancer drug. In the commercialized paclitaxel prod-
uct (Taxol®), Cremophor EL is used to solubilize the drug. Unfortunately, Cremophor EL itself is
toxic, which makes finding a suitable alternative highly in need. Moreover, the circulation time of
Taxol® is very short. Coating the nanocarriers (e.g., liposomes) with hydrophilic polymers such as
polyethylene glycol (PEG) has been established as a strategy to prolong circulation of the nanocar-
rier-entrapped molecules in the blood by making the carrier highly evasive to uptake by the blood
macrophages
[17,18]
. PEGylation of paclitaxel has longer circulation time in the blood than Taxol®
[19]
. Functionalized SWNTs were conjugated with paclitaxel through branched PEG chains via a
cleavable ester bond. The resultant formulation was more efficient in suppressing tumor growth
in
vivo
than Taxol® or paclitaxel-PEG conjugate in a 4T1 breast cancer animal model. The PEGylated
nanotubes were able to prolong the circulation and greatly enhance cellular uptake of the drug by
the cancer cells
[20]
. Similar findings of anticancer activity have been recently shown when pacli-
taxel was loaded into PEGylated SWNTs or MWNTs using HeLa cells and MCF-7 cancer cell lines
[21]
. Multidrug resistance is a significant obstacle to successful anticancer drug therapy since the
P-glycoprotein efflux transporter can interfere with the accumulation of anticancer drugs in the tar-
get cells, resulting in reduced effectiveness of therapy
[22,23]
. Recently, using hepatoma cell lines,
PEGylated MWNTs have been shown to accumulate in multidrug resistant cells as efficient as in
nonresistant cells as observed by confocal microscopy
[24]
. Interestingly, Liu and coworkers
[25]
reported that although PEGylation of SWNTs can prolong blood circulation time, it may cause an
accumulation of the nanotubes in the dermal tissues of mice, suggesting that the degree of coating
with PEG should be optimized.
Similar to FA receptors, biotin receptors might be overexpressed on the surfaces of cancer cells.
Therefore, biotin-functionalized SWNTs conjugated with the anticancer agent taxoid using a cleav-
able linker have been designed
[26]
. The drug was transported via endocytosis, released in the cell
and interacted with microtubules as evaluated by flow cytometry. This resulted in the formation of a
stable microtubule-taxoid complex and finally caused apoptosis and cell death (
Figure 20.5
).
A targeted delivery system of FA-tethered SWNTs-doxorubicin (DOX) has been designed.
Bioadhesive polymers such as chitosan (CHI) and sodium alginate (ALG) were included to enhance
the aqueous dispersability of the nanotubes while FA was used to improve the targeting properties of
