Biomedical Engineering Reference
In-Depth Information
Fe
2
O
3
nanoparticles. The fi rst method (direct copolymerization) led to low amounts
of grafted polymer due to diffusion limitations. However, in the second method
(inverse emulsion polymerization) the local concentration of the macromonomer
surrounding the aggregates of silylated Fe
2
O
3
nanoparticles was increased and, as
a result, the amount of surface-immobilized polymer was greatly increased. In this
way, hybrid particles (
∼
100 nm) containing up to 8 g of polymer per gram Fe
2
O
3
were achieved.
Poly(
L
- Lysine) Coating
MNPs have recently been deemed to be an attractive agent
for the labeling of stem cells. Iron oxide nanoparticles have been modifi ed with
poly(
L
-lysine) for this purpose, and demonstrated a higher effi ciency of intracel-
lular uptake by mesenchymal stem cells (MSCs) in comparison with a commercial
contrast agent, Endorem (dextran-coated MNPs) [52]. In these studies, magnetite
prepared by the coprecipitation method was treated with sodium citrate and oxi-
dized to maghemite by sodium hypochlorite to enhance the redox stability. The
addition of poly(
L
-lysine) solution to the iron oxide resulted in an ionic interaction
between the positive charges of the amine groups at the end of the poly(
L
- lysine)
side chains and the citrate complexed on the iron oxide surface. The hydrodynamic
diameter of the nanoparticles ranged from
∼
80 to 240 nm, depending on the poly(
L
-
lysine)/
- Fe
2
O
3
ratio, and showed a signifi cant increase after 5 months of storage
due to particle aggregation. The zeta potential of the particles (between
γ
−
40 and
−
- Fe
2
O
3
ratio, indicating that the
negatively charged surface was compensated for by the positively charged poly(
L
-
lysine). The latter was strongly associated with the iron oxide nanoparticles, and
not released into cell culture medium. The results of both rat and human MSC
labeling with the poly(
L
- lysine) - modifi ed maghemite nanoparticles showed that the
degree of iron oxide internalization by the cells increased at higher poly(
L
- lysine)
concentrations, and that the cells took up signifi cantly more poly(
L
- lysine) - modi-
fi ed nanoparticles than Endorem. The effi ciency of cell labeling also increased with
the M
w
of the poly(
L
-lysine) up to 388 100 Da, which can be considered an optimum
poly(
L
- lysine) M
w
for
46 mV) increased with increasing poly(
L
- lysine)/
γ
- Fe
2
O
3
nanoparticle modifi cation. The
in vitro
MR imaging
of labeled cells, and the
in vivo
MR imaging of rat brain with implanted labeled
cells, indicated that both the higher
r
2
relaxivity of poly(
L
- lysine) - modifi ed nanopar-
ticles and their better internalization in the cells as compared to Endorem would
enable an easier MRI detection and tracking of stem cells in tissues after trans-
plantation. Cellular uptake of the poly(
L
- lysine) - modifi ed iron oxide was deemed
to be facilitated by its interaction with the negatively charged cell surface. However,
since anionic nanoparticles can also be effectively taken up by cells (see Section
10.3.1), the nature of the surface charges on the MNPs may be only one factor
among many which affect nanoparticle internalization by cells.
γ
Coating with Temperature - Responsive Polymers
Temperature - responsive poly-
mers have been designed to encapsulate the MNPs and drug molecules at below
body temperature such that, upon exposure to a temperature equivalent to or
slightly higher than normal body temperature (37 °C), the polymer would undergo
