Biomedical Engineering Reference
In-Depth Information
adhesion to the HAECs was enhanced as a result of the upregulation of expres-
sions of ICAM-1 and IL-8. The U937 phagocytosized the NMs which simul-
taneously provoked oxidative stress and severe endothelial cell toxicity. This
study indicated that i.v.-administered IOMNPs may result in endothelial inflam-
mation and dysfunction when NMs escape phagocytosis and directly interact
with the endothelial layer, or the IOMNPs undergo phagocytosis by monocytes
followed by their dissolution resulting in free iron ions, or they undergo phago-
cytosis and induce oxidative stress responses. 170 Cell death that were most likely
due to oxidative stress were observed in polyol-produced maghemite γ-Fe 2 O 3
NPs that were efficiently internalized by human endothelial cells within 24h of
exposure. 191 These NMs were rapidly cleared through the urine but caused tox-
icity in the liver, kidneys, and lungs and did not affect the brain and the heart. 170
From these studies, it can be inferred that care must be taken with respect to sur-
face coating, cellular targeting, and local exposure toward clinical applications.
Ferritin contains 7-nm iron (ferrous) particles and a protein shell that had
failed to induce spontaneous glutamate release but induced intrasynaptosomal
ROS formation that was insensitive to the inhibitor of NADPH oxidase, DPI
(diphenyleneiodonium), and to carbonyl cyanide m-chloro phenyl hydrazone
CCCP, a mitochondrial uncoupler. 192 As more applications of IOMNPs are stud-
ied, concerns about long-term toxicity related to the production of toxic-free iron
during their biodegradation prompted an EM-based study which found that the
iron oxide NPs were degraded after internalization by macrophages, leading to
the core iron being incorporated into the nontoxic iron-storing protein, ferritin. 193
5.9.5   Nanotubes
Previously, it has already been possible to attach drug molecules directly to
antibodies; however, attaching a handful of drug molecules to an antibody sig-
nificantly limits its targeting ability because the chemical bonds that are used
for the drug attachment deactivates antibody activity. With the onset of nano-
technology, a number of NPs have been investigated to overcome this limi-
tation. Among the NMs available commercially, carbon nanotubes have been
studied quite well. Tumor targeting single-walled carbon nanotube has been
developed by covalently attaching tumor-specific mAbs, radiation ion chelates,
and fluorescent probes. 194 This led to a new class of anticancer compound that
contains both tumor-targeting antibodies and NPs called fullerenes (C60) that
can be loaded with several molecules of an anticancer drug such as Taxol ® . 195
This system allows loading as many as 40 fullerenes onto a single skin can-
cer antibody called ZME-108 that can be used to deliver drugs directly into
melanomas. Distinct sites on the antibody are hydrophobic which attract the
hydrophobic fullerenes in large numbers and so multiple drugs can be loaded
into a single antibody in a spontaneous manner, requiring no covalent bond, so
the increased payload does not significantly change the targeting ability of the
antibody. The fullerene-based therapies provide potential to carry multiple drug
Search WWH ::




Custom Search