Biomedical Engineering Reference
In-Depth Information
labeled leukocytes, lymphocytes, and monocytes with SPIOs in an attempt to study
immune tracking. However, because these nanoparticles were internalized very
slowly, it became necessary to attach targeting vectors. For example, HIV- 1 Tat
peptide carries a transmembrane and a nuclear localization signal within its
sequence [71], and is therefore capable of translocating exogenous molecules into
cells. The conjugation of HIV-1 Tat peptide into dextran-crosslinked iron oxide
nanoparticles has been shown to increase their uptake over 100-fold into lympho-
cytes when compared to bare nanoparticles [72, 73]. In addition, anionic maghemite
nanoparticles (AMNPs) have been shown to have a cell internalization rate com-
parable to that of dextran-coated iron oxide nanoparticles [74]. This is because the
particles' negative surface charge interacts strongly and nonspecifi cally with the
cell's plasma membrane (even if the net surface charge of the membrane is nega-
tive, there are also positive sites within it that attract the agent). This increase in
internalization substantially increases the detectability of labeled cells by MRI, and
consequently increased its ability to isolate and sort cells from tissues following
in vivo
experiments such as transplantations.
Magnetic nanoparticles have also been used for transgene expression with MRI.
Other imaging modalities, such as optical and nuclear imaging, have been used
to image transgene expression, although the relatively low resolutions or limited
depths of penetration of these modalities limits their effectiveness. Although the
use of magnetic nanoparticles to image transgene expression is still in its early
stages, the results of preliminary studies have demonstrated the feasibility of using
MRI to depict the activity of endocytotic receptors, such as the asialoglycoprotein
receptor [75, 76]. Human transferrin, which serves as a ligand for the endocytotic
transferrin receptor, has been conjugated to monocrystalline iron oxide to image
transgene expression using MRI [77, 78]. A universal MRI marker gene to image
gene expression may enable research groups to monitor gene therapy in which
exogenous genes are introduced into the body so as to eliminate a genetic defect,
or to add an additional gene function to the tumor cells. Currently, investigations
in this area are leading to the development of techniques that can be used to
visualize noninvasively where, when, and in some cases at what level, a gene is
being expressed.
7.4
Applications: Hyperthermia and Thermal Ablation
The use of heat for the preferential killing of cancer cells, whether through
hyperthermia or thermal ablation, represents a very promising approach to
cancer therapy. This method is especially appealing because it is a physical
treatment, and therefore there are fewer side effects compared to conventional
cancer treatment strategies such as radiotherapy and chemotherapy. Both, hyper-
thermia and thermal ablation can also be performed repeatedly without any
accumulation of toxic side effects. Hyperthermia is defi ned as the heating of
tissues at 42-46°C [79], while thermal ablation is the heating of tissues at
