Biomedical Engineering Reference
In-Depth Information
imaging contrast agents, both
in vitro
and
vivo
[6, 242 - 244] . Examples have also
been described of single cell detection in small animals, using MRI [245].
It was noted above that a number of clinical MRI applications are based on the
uptake of standard nanoparticulate MRI agents by the cells of the RES (e.g., mac-
rophages). Consequently, a signifi cant amount of research has been focused on
the investigation of various commercially available USPIO and SPIO contrast
agents in macrophages, glioma cells, leukocytes, and lymphocytes [246 - 250] .
Numerous reports have also been made on the labeling of mesenchymal stem
cells with various superparamagnetic nanoparticles, and their subsequent
in vitro
and
in vivo
tracking by MRI [251-260]. It has been shown that nanoparticle-labeled
human CNS stem cells can survive over the long term and differentiate in a site-
specifi c manner identical to that seen for transplants of unlabeled cells [261]. This
has enabled a series of important studies to be performed
in vivo
using nanopar-
ticle-labeled cells. For example, embryonic stem cells were labeled with a USPIO
MRI contrast agent, using a lipofection procedure, and implanted into rat brains.
Subsequently, it was found that, over a certain period of time, the cells migrated
and massively populated the border zone of the damaged brain tissue on the
hemisphere opposite to the implantation sites. In these studies, MRI demon-
strated an excellent capability for the noninvasive observation of cell migration,
engraftment, and morphological differentiation, with high spatial and temporal
resolution [262] .
Reports have also been made on the use of commercially available SPIO and
USPIO magnetic labeling of human dermal fi broblasts [263, 264], HeLa cells [265],
dendritic cells [266, 267], and human umbilical vein endothelial cells (HUVECs)
[268] .
Unfortunately, most of the above-described approaches are passive and rely
entirely on the endocytosis of commercially available magnetic nanoparticles -
which occasionally do not demonstrate suffi cient cellular uptake. In order to
increase the uptake of magnetic nanoparticles and provide specifi c targeting, the
nanoparticles must be functionalized (or vectorized) with appropriate peptides,
monoclonal antibodies, or proteins [157, 269 - 271] .
In some cases, the cellular uptake of commercial nanoparticulate contrast agents
(e.g., ferumoxides) can be improved by simply mixing the nanoparticles with
appropriate transfection agents, such as dendrimers, high- molecular - weight poly -
L-lysine, lipofectamine, or protamine sulfate [6, 199, 243, 247].
Several covalent approaches have been employed to improve particle uptake,
depending on the cell type and structure. Signifi cant efforts have also been focused
on the specifi c targeting of cancer cells. For example, the conjugation of magnetic
nanocrystals to a cancer-targeting antibody (herceptin) has allowed the specifi c
labeling of human cancer cells and their
in vivo
monitoring in live mice by MRI
[167]. Several reports also exist on the conjugation of magnetic nanoparticles to a
peptide sequence from the transactivator protein (Tat) of HIV- 1 [102 - 104, 272] , and
their investigation in T cells both
in vitro
and
in vivo
in live mice. In another study,
magnetic nanoparticles were coupled to anti- Her - 2/neu antibodies or gamma
globulin IgG and used for the detection of Her- 2/neu - expressing tumor cells
in vitro
