Biomedical Engineering Reference
In-Depth Information
polymers [molecular weight (M
w
)
40 000 Da] to yield a suspension of dextran-
coated ferromagnetic (Fe
3
O
4
) colloidal particles. Dextran, which is deemed to be
noncytotoxic, is one of the most common coatings used for MNPs. By using TEM,
the iron core was seen to range in size from 10- 20 nm, while the dextran - coated
particles were roughly spherical in shape, with a diameter of 40 nm. The dextran-
coated particles contained 50% by weight Fe, were stable in physiological buffers,
and did not aggregate over a pH range of 3-10. The use of dextran polymers with
M
w
ranging from 10 000 to 70 000 Da in the reaction resulted in particles which
exhibited similar properties. On the other hand, the blood half-life and biodistribu-
tion of the MNPs were shown to be infl uenced by the various synthesis conditions
[19]. Iron oxide nanoparticles prepared by precipitation, with subsequent dextran
adsorption onto the particle surface, generally demonstrated shorter half- lives than
those prepared by particle formation in the presence of dextran. Furthermore,
synthesis conditions such as pH and temperature affected the structure of the
surface-bound dextran. The longest circulation times were achieved by MNPs
covered by a relatively dense brush of dextran molecules that protected the iron
oxide core against contact with blood proteins and phagocytosis- associated
receptors.
Experiments conducted with human fi broblasts indicated that the dextran-
coated particles were taken into the cells probably through fl uid phase endocytosis,
and the cell behavior was adversely affected by this internalization; this resulted
in possible apoptosis, aberrations in cell morphology, and resultant decreases in
cell motility [20]. A recent report included investigations into the possible acute
toxicity and irritation of dextran-coated MNPs injected subcutaneously into the
tissues of mice [21]. The LD
50
dosage (single treatment) for death to occur within
2 weeks was found to be
∼
4410 mg kg
− 1
, whereas the injection of 0.3 ml of 10%
dextran-coated MNPs fl uid [containing 30 mg particles in 50% (w/v) aqueous
dextran solution] induced reversible effects that were well tolerated by mice. Fur-
thermore, a crosslinked dextran coating on the MNPs was reported to be nonbio-
degradable [4] .
Among the various types of dextran-coated MNP, differences in the functional
group of the shell polymer can have a signifi cant effect on the effi cacy of cell label-
ing. This was illustrated by a recent study which compared the feasibility and
effi ciency of labeling human mesenchymal stem cells (MSCs) and human cervix
carcinoma (HeLa) cancer cells with two commercially available MNPs, Feridex and
Resovist [22]. Both nanoparticle preparations have superparamagnetic cores of
10-12 nm embedded in a biocompatible polymer, yielding particles of a hydrody-
namic diameter of 70-150 nm. However, Resovist comprises magnetite nanopar-
ticles stabilized by carboxydextran, while Feridex is coated with nonfunctionalized
dextran. For MSC labeling, Resovist was found to be a suitable agent, without the
need for a transfection agent, and was more effi cient than Feridex. In the case of
the HeLa cells, Resovist was still effective, but the uptake of Feridex was very low.
This difference in uptake behavior was attributed to the presence of carboxyl
groups in Resovist. Under physiological conditions (pH 7.4), the carboxydextran
is expected to be mainly in the deprotonated form, that is, negatively charged. The
∼
