Biomedical Engineering Reference
In-Depth Information
Abdelhalim
38 - 41
conducted a series of
in vivo
experiments to evaluate the effects of GNPs on the
cardiovascular system. 10 μg of GNPs of various particle sizes (10, 20, and 50 nm) were intraperito-
neally administered to Wistar-Kyoto rats for 3 or 7 days. The disruption of the central vein intima
of the hepatic tissues was observed in rats that received 10 and 20 nm GNPs, while less disruption
was observed in rats that received 50 nm GNPs. It was also found that more damage was detected if
the GNP exposure increased from 3 to 7 days. The above observations suggested the potential endo-
thelial damage and vascular stress by GNPs exposure.
41
GNPs were also found to result in size- and
time-dependent histological alterations of the heart tissues, with smaller size and longer exposures
induced a higher degree of heart muscle disarray, foci of hemorrhage, scattered cytoplasmic vacu-
olization, and congested and dilated blood vessels.
38
Similar results were found in another study
where GNPs of smaller sizes (10 and 20 nm) induced the congestion of the heart muscle in rats, but
rats treated with 50 nm GNPs demonstrated benign, normal-looking heart muscle.
40
The author also
found that GNPs of smaller sizes decreased the blood plasma viscosity to an even lower level than
the larger size did, which may be attributed to decreases in hematocrit and hemoglobin concentra-
tions in addition to erythrocyte deformabilities.
39
It could be concluded from Abdelhalim's work
that GNPs caused size- and time-dependent cardiovascular toxicities when intraperitoneally admin-
istered to rats, with a smaller size and longer exposure that caused a more severe effect. A number of
literatures have reported the biodistribution of variously sized GNPs. Smaller particles were found
to be present in more organ systems and in higher levels than their larger counterparts were,
42,43
which might partly explain Abdelhalim's observations.
On the other hand, the absence of GNP-induced cardiovascular toxicity was observed in other
in vivo
studies using mice or zebrafish embryos as models. Thakor et al.
44
synthesized Raman-active
PEGylated silica-coated GNPs. They examined the toxicity of the GNPs after IV administration
in mice and found no changes in the electrocardiogram (ECG), blood pressure, or heart rate for 2
weeks. In addition, all plasma biochemical and hematological indices remained within their normal
ranges. The differences in results from Abdelhalim's study might be due to the different administra-
tion routes and the different surface coatings of the nanoparticles. GNPs showed good biocompat-
ibility in the zebrafish embryo model. Asharani et al.
45
examined the cardiovascular effects of GNPs
(15-35 nm) at six different concentrations (10, 25, 50, 75, and 100 μg/mL) in zebrafish embryos, and
found that GNPs did not result in pericardial edema or heart rate changes even after 72 h of incuba-
tion at the highest tested concentration. Wang et al.
46
evaluated the biocompatibility and toxicity of
the surface-enhanced Raman scattering (SERS) GNPs by injecting around 3 × 10
6
particles into the
embryonic cell at the one-cell stage. The SERS GNPs injected 7-day-old zebrafish embryos showed
proper form and function of the heart and vasculature, indicating no toxic effects on the cardiovas-
cular systems.
In an
in vitro
study, Freese et al.
47
found that 15 sequentially modified GNPs based on three
different core sizes (18, 35, and 65 nm) and five polymeric coatings remained nontoxic to primary
human dermal microvascular endothelial cells (HDMECs) up to 48 h at 250 μg/mL, the highest
concentration tested. However, there was no group treated with the unmodified GNPs; thus, the
results need to be interpreted with caution.
12.2.3.2 Iron Oxide Nanomaterials
Iron oxide nanomaterials, mainly existing as magnetite (Fe
3
O
4
) and hematite (α-Fe
2
O
3
and γ-Fe
2
O
3
)
nanoparticles, have attracted an extensive interest in their application in terabit magnetic storage
devices, pigments, catalysts, sensors, high-sensitivity biomolecular magnetic resonance imaging,
drug and gene delivery, and labeling macromolecules and cells.
48
The increased production and
use of iron oxide nanoparticles inevitably results in a greater exposure risk for both people and the
environment. Studies regarding the cardiovascular effects of iron oxide nanomaterials were mostly
focused on
in vitro
studies, using various types of cell models including endothelial cells, embry-
onic stem cells (ESCs), and cardiac myocytes.
