Biomedical Engineering Reference
In-Depth Information
toxicity based on the reports to date. Galagudza et al.
28
infused SNP suspensions (6-13 nm) into
male Wistar rats through the femoral vein at a dose of 0.7 mg/100 g body weight, and recorded the
hemodynamic parameters at the end of infusion. Mild changes in hemodynamic parameters, such as
heart rate, mean arterial pressure (MAP), and pulse arterial pressure were observed, indicating the
lack of acute toxicity from the tested nanoparticles. Nishimori et al.
29
found no histological injury
in mice hearts after the chronic IV injection (twice a week for 4 weeks) of 70-nm silica particles.
A more comprehensive study conducted by He et al.
30
revealed that intravenously injected MSNs of
various particle sizes (80, 120, 200, and 360 nm) induced no pathological changes in major organs,
including the heart, after 1 month, yielding good compatibility. Huang et al.
31
recorded hematology
markers 24 h and 18 days after the IV injection of differently shaped MSNs. All hematology marker
values were mostly within normal ranges and did not indicate a trend of toxicity associated with
shape, indicating a good compatibility. The absence of cardiovascular toxicity from SNPs upon IV
administration might be explained by their low accumulation in the heart.
30
Kumar et al.
32
prepared
multimodal, organically modified SNPs with diameters of 20-25 nm. It was found that <5% of the
total dose accumulated in the heart upon IV injection, was much less than in the liver and spleen.
Several
in vitro
studies have been performed to evaluate toxic effects on the cardiovascular
system. The underlying, molecular mechanisms were revealed with the help of these
in vitro
mod-
els. Intravenously injected SNPs are directly exposed to the endothelial cells; thus, it is of interest
to investigate the biological effects of SNPs on the endothelial cells. Liu et al.
33
found that SNPs
(20 nm) markedly induced dysfunctions (ROS production, mitochondrial depolarization, and apop-
tosis) in human umbilical vein endothelial cells (HUVECs) 24 h after exposure, with the concentra-
tion ranging from 50 to 200 μg/mL; these effects were through oxidative stresses via the JNK, p53,
and NF-κB pathways, suggesting a significant risk for the development of cardiovascular diseases
such as atherosclerosis and thrombus. Corbalan et al.
34
found that SNPs (10, 50, 150, and 500 nm)
induced platelet aggregation when incubated with isolated human platelets. Furthermore, the effects
were inversely proportional to their sizes.
34
Mechanistic studies revealed that amorphous SNPs pen-
etrated the platelet plasma membrane and stimulated a rapid and prolonged NO release, followed by
the activation of the glycoprotein IIb/IIIa (GPIIb/IIIa), the expression of the selectin P (SELP) on
the platelet surface membrane, and the aggregation of platelets.
34
An alveolar-capillary coculture
model was used to evaluate the possible hazards of amorphous SNPs encountering the principal
biological barrier in the lower respiratory tract.
35
The epithelial cell line, H441, and the endothelial
cell line, ISO-HAS-1, were cocultured on the opposite sides of a filter membrane to mimic the
alveolar-capillary barrier. It was found that the endothelial cell line (ISO-HAS-1) seemed to be
more sensitive to exposure to SNPs than the epithelial cell line (H441) in terms of cell viability and
the release of lactate dehydrogenase (LDH). Furthermore, cocultures showed a release of IL-6 and
IL-8 even at concentrations that were 10-100-fold less than the toxic concentrations, indicating
early inflammatory events in pulmonary alveoli after SNP inhalation.
35
It could be concluded that
in vitro
models were more sensitive than the
in vivo
models in detecting the adverse effects on the
cardiovascular system.
12.2.3 M
etallIc
N
aNoMaterIals
12.2.3.1 Gold Nanomaterials
Recently, gold nanoparticles (GNPs) are being increasingly parenterally administered to animals
and humans as carriers for the delivery of drugs, genetic materials, antigens, and diagnostic agents.
Meanwhile, concerns were raised about the possible toxicity of these engineered GNPs to the
organisms. Several review papers have been published regarding the
in vivo
and
in vitro
toxicity of
GNPs.
36,37
However, special attention has not yet been paid to their cardiovascular toxicities. A sum-
mary of recent data about the adverse effects of GNPs on the cardiovascular systems are presented
below.
