Biomedical Engineering Reference
In-Depth Information
and in animal tumor models, and this in turn allowed the recognition of a distinct
decrease in the normalized MR signal ratio between the tumor and a reference area
[273]. The conjugation of magnetic nanoparticles to folic acid for targeting specifi c
folate receptors in cancer cells has also been reported [74, 94, 274, 275]. One inter-
esting new approach was that reported by Kohler
et al.
[276], who developed conju-
gates of iron oxide nanoparticles and methotrexate (a chemotherapeutic drug).
These conjugates could be used as both contrast agents for diagnostics and as drug
delivery systems for cancer therapy. Other studies have involved the targeting and
in vivo
tracking of cancer cells using ovalbumin-specifi c splenocytes (OT-1) labeled
with magnetic nanoparticles [277], and also lymphocytes and 9L rat gliosarcoma
labeled with a ferumoxide- protamine sulfate complex [278] .
4.5.2.2
Molecular Imaging
In general, “molecular imaging” refers to the
in vivo
noninvasive imaging of tar-
geted biomolecules or targeted cells and biological processes in living organisms
[6, 279, 280]. For molecular imaging, MRI is one of the best available techniques,
with the imaging agents being based on the recognition of unique cell-surface
biochemical signatures. In this case, the use of magnetic nanoparticulate MRI
agents can offer the opportunity not only for targeted diagnostic studies but also
for image- monitored, site - specifi c therapeutic delivery, much like the “magic
bullet”. This combination of rational targeted diagnostic and therapy is expected
to result in new clinical approaches to the treatment of many diseases [279].
Nanoparticulate contrast agents can be accumulated within a biological site by
either passive or active targeting mechanisms.
•
Passive targeting
contrast agents concentrate in the phagocytic cells (e.g.,
macrophages, Kupffer's cells) and corresponding organs (liver, spleen, lymph
nodes, etc.) that are responsible for particle clearance from the body. Passive
targeting using commercially available nanoparticulate MR contrast agents (see
Table 4.1) has mostly been considered above in clinical applications.
•
Active targeting
contrast agents require conjugation to specifi c ligands
(pharmacophores), which then enables a targeted, site-specifi c accumulation
of the agents. Typical ligands for targeting include antibodies, peptides,
polysaccharides, aptamers, and drugs. As discussed above for vectorization,
these ligands can be linked to magnetic nanoparticles either covalently or
noncovalently.
To date, most MR contrast agent applications have been based on passive target-
ing. However, intensive research is currently being undertaken on the develop-
ment of targeted magnetic nanoparticles, which have been evaluated in animal
models, both
in vitro
and
in vivo
.
A large proportion of this research has been focused on the use of magnetic
nanoparticle conjugates in targeted cancer imaging. For example,
3
integrin -
targeted magnetic nanoparticles have been used for the specifi c ultrasensitive MRI
detection of small regions of angiogenesis associated with minute solid tumors
α
V
β
