Biomedical Engineering Reference
In-Depth Information
in Table 17.2, but there are many other studies available, for a wide
range of magnetic nanoparticle systems.
(WiDr), malignant human glioma (RuSi-RS1), and normal human
cerebral cortical neuronal (HCN-2) cells. Cells were grown in
medium containing one of two types of magnetite nanoparticles,
both at a concentration of 0.6 mg/ml. The first (#P6) consisted of
3.3 nm diameter cores with a dextran coating for a total hydro-
dynamic diameter of 50 to 70 nm with a negative surface charge.
The second (#BU48) featured 13.1 nm diameter cores coated with
aminosilane, for a total hydrodynamic diameter of 17 nm with
a positive surface charge. Biocompatibility had been previously
demonstrated for both particles. Uptake concentrations and cel-
lular distribution were determined after 0, 6, 24, 48, 72, 144, 168,
and 192 hours. Intracellular iron concentration was characterized
by magnetophoresis and a colorimetric iron assay. Intracellular
uptake was characterized by TEM, and surface attachment was
characterized by SEM. Time-dependent uptake for two of the cell
lines is summarized in Figure 17.8. The wide variety of uptake
trends is apparent. The fibroblast cells demonstrate the most sig-
nificant uptake. However, the uptake profiles vary significantly
between the two nanoparticles. The #P6 nanoparticles exhibit
high initial uptake followed by more gradual uptake through 192
hours. The #BU48 nanoparticles show low initial uptake, with a
sharp peak in intracellular concentration around 168 hours, fol-
lowed by a steep decline (which was attributed to exocytosis). All
the cell lines demonstrated measurable iron uptake.
TEM indicated intracellular nanoparticles were contained in
phagosomes or lysosomes. The #P6 particles often occurred as
aggregates, which was due to the loss of their dextran coating in
17.4 Biological Effects
A nanoparticle's surface coating is a major determinant for biologi-
cal interactions and pathways. Upon administration into the body,
the surface chemistry, in combination with size and geometry,
determines which biological proteins adsorb to the particle surface,
which in turn largely determines subsequent biological process-
ing (Aggarwal et al. 2009). On the cellular level, the nanoparti-
cle coating also determines the mechanism of cellular uptake.
Nanoparticles are generally internalized through direct interaction
with membrane-embedded receptors or indirectly through asso-
ciation with the membrane lipid bilayer (Chou, Ming, and Chan
2010). Both processes result in some form of endocytosis, in which
the nanoparticles are internalized into a membrane-bound vesicle.
Specialized cells, including macrophages, monocytes, and neutro-
phils, can also internalize particles through phagocytosis.
17.4.1 Effects of Nanoparticle Surface Coating
Nanoparticle coating and cell type have been shown to have
a major impact on uptake of iron oxide nanoparticles
in vitro
(Jordan et al. 1999). Jordan et al. demonstrated differential endo-
cytosis of dextran- and silane-coated magnetite nanoparticles
in
vitro with normal human fibroblasts, colonic adenocarcinoma
(a)
(b)
600
600
500
500
400
400
300
300
200
200
100
100
0
0
0624 48
Growth time (h)
72
144
168
192
0624 48
Growth time (h)
72
144
168
192
600
600
500
500
400
400
300
300
200
200
100
100
0
0
0624 48
Growth time (h)
72
144
168
192
0624 48
Growth time (h)
72
144
168
192
FIGURE 17.8
Time-dependent intracellular iron concentration for fibroblast (a) and malignant glioma (b) cells. (From Jordan, A. et al.,
Journal
of Magnetism and Magnetic Materials
194, 1, 1999.)
