Biomedical Engineering Reference
In-Depth Information
demonstrated marked tumor suppression that were comparable to the effect of
Doxil and superior to free dox.
Super paramagnetic iron oxide particles can be used in conjunction with
MRI to localize the tumor as well as for subsequent thermal ablation. This has
been used, for example, to target glioblastoma multiforme (GBM), a primary
malignant tumor of the brain with few effective therapeutic options. The pri-
mary difficulty in treating GBM lies in the difficulty of delivering drugs across
the BBB. However, nanoscale liposomal iron oxide preparations were recently
shown to improve passage across the BBB.
183
Alexiou et al.
184
reported the successful preclinical applications of iron-
based NP drug delivery systems. He and his group established the established
initial parameters for targeted MNP drug delivery using intratumor arterial
(i.a.) administration.
176,184,185,186
In their studies, an external magnetic field was
applied to make i.a.-administered ferrofluids (100-nm diameter NPs) loaded
with mitoxantrone (MTX) to accumulate at rabbit hind limb VX2 tumors fed
by this artery. The ferrofluids consisted of iron oxides and hydroxides NPs that
were encapsulated with a starch polymer matrix to provide biological stabil-
ity with sites for chemoabsorptive/electrostatic MTX binding, forming MTX-
NMs. Immediately after administration of the MTX-NMs, darkened tumor
blood vessels were observed histologically with brown-black particles distrib-
uted throughout the entire tumor. At the end of a 3-month study, no tumor tissue
was histologically observed in rabbits that were i.a. treated with the MTX-NMs
but the i.v. administration failed. This may have been caused by the extensive
clearance of NMs prior to reaching the tumor or to premature MTX release
before extravasation. This approach is currently being studied for the treatment
of head and neck cancer.
187
The extensive applications of iron-based NPs for drug delivery and other
medical applications that spurred extensive toxicological assessments have been
conducted by various researchers. In vitro studies using human aortic endo-
thelial cells (HAECs) were incubated with different NPs composed of Fe
2
O
3
,
Y
2
O
3
, or ZnO after which the levels of messenger RNA and protein levels of
intercellular adhesion molecule-1 (ICAM-1), IL-8, and monocyte chemoattrac-
tant protein-1 (MCP-1) were evaluated.
188
The interactions of the NPs with the
cells were evaluated with inductively coupled plasma mass spectrometry and
TEM. The results showed that all three NPs were internalized and localized to
intracellular vesicles in HAECs. Out of the three NMs, Fe
2
O
3
did not induce
an inflammatory response unlike Y
2
O
3
and ZnO NPs that did. In a separate
investigation, both Fe
2
O
3
and Fe
3
O
4
NMs generated oxidative stress as well as
increased nitric oxide (NO) production in human ECV304 umbilical endothe-
lial cells.
189
Early signs of apoptosis such as loss of mitochondrial membrane
potential and nuclear chromatin condensation were apparent.
The effect of 22- to 43-nm Fe
2
O
3
NPs on HAECs and U937 resulted in cyto-
plasmic vacuolation, mitochondrial swelling and cell death that were accompa-
nied by an increase in NO production and NO synthesis activity.
190
Monocytes
