Biomedical Engineering Reference
In-Depth Information
10.3.1.5 Triethylene Glycol - Coated MNP s via the High - Temperature
Decomposition Method
Another example of the one-pot synthesis of water-soluble MNPs using the high-
temperature decomposition of Fe(acac) 3 is to use triethylene glycol (TEG) as the
reaction medium. Here, TEG played a triple role as a high-boiling point solvent,
reducing agent, and stabilizer to effi ciently control the particle growth and prevent
interparticle aggregation [33, 34]. The size of the MNPs from TEM images was
8 nm, while the hydrodynamic diameter of the particles in water was 16.5 nm.
The cellular uptake of TEG-coated magnetite nanoparticles was investigated with
rat C6 glioma cell line and control normal neural cells. Prussian blue- staining
experiments indicated that, after a 4 h incubation with 100
g Fe ml − 1 of the TEG-
coated magnetite nanoparticles, 99.6% of the C6 cells were stained whereas no
blue spots were observed in the cytoplasm of control normal neural cells treated
under the same conditions. The high uptake of TEG-coated magnetite nanopar-
ticles in the C6 glioma cell line was attributed to a strong interaction between the
MNPs and C6 glioma cells that might arise from the unusual metabolic activity
of cancer cells, and also from an ultra-small size effect of the MNPs. A subsequent
cell viability assay using MTT (3 - (4,5 - dimethylthiazol - 2 - yl) - 2,5 - diphenyltetrazolium
bromide) indicated that incubation with these MNPs (up to 200
μ
μ
g Fe ml − 1 for 24 h)
did not affect the viability of either C6 or normal neural cells.
10.3.1.6 4 - Methylcatechol - Coated MNP s via High Temperature
Decomposition Method
Finally, an example is given of a combination of the one-pot method to introduce
an anchoring group on the MNP surface, and thereafter conjugation with
the functional molecule. In this case, the coating was not a polymer but rather
a peptide. Fe 3 O 4 MNPs of 4.5 nm were synthesized by the thermal decom-
position of iron pentacarbonyl (at 220 °C) in benzyl ether in the presence of
4-methylcatechol as surfactant, followed by air oxidation [35]. A coating of 4-
methylcatechol was formed on the MNP surface as a result of the strong chelation
bond between iron and the catechol unit. The aromatic ring of 4-methylcatechol
on the MNPs was utilized to couple with the amine group of a cyclic RGD
peptide, via the Mannich reaction in the presence of formaldehyde in dimethyl-
formamide (DMF). The number of RGD peptides per particle was estimated as
100-200, while the overall size of the particles (measured by DLS in water)
was
8.4 nm. The RGD-coated MNPs were stable for several months in aqueous
dispersion, without precipitating. Following incubation of the RGD- coated MNPs
with U87MG human glioblastoma (high
α
v
β
3 integrin level) and MCF-7 human
breast cancer (low
3 integrin level) cell lines at 37 °C for 30 min, the Fe
uptake for U87MG cells was approximately fi vefold higher than that of MCF-7
cells. This demonstrated the integrin specifi city of the RGD-coated MNPs. The
inhibition of RGD-coated MNPs uptake by U87MG cells in the presence of a
blocking dose (2
α
v
β
M ) of the cyclic RGD peptide further confi rmed the specifi city
of MNPs. The r 2 relaxivity of these MNPs was measured as 165 m M − 1 s − 1 , which
was larger than that of the commercial Feridex nanoparticles (104 m M − 1 s − 1 ) with
μ
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