Iron Oxide Nanoparticles and Derivatives for Biomedical Imaging and Application in Cancer Diagnosis and Therapy - Bioanalysis Advanced Materials Methods and Devices - page 5

passive targeting of different cancer types such as prostate, bladder, penile,
and testicular cancer as well as renal neoplasm [ 24 ].
Non-invasive imaging is the central rationale for using unconjugated iron
oxide nanoparticles. Passive targeting has been used to assess the extent of lymph
node metastasis in prostate cancer patients in clinical studies using lymphotropic
superparamagnetic nanoparticles [ 13 ]. These studies have shown that with these
magnetic nanoparticles, detection of small metastases or otherwise undetectable
metastases (by other noninvasive means) is now possible by high-resolution MRI.
There are very mild side effects associated with these nanoparticles. Even the
patients within high-risk groups such as cardiovascular, renal, and hepatic diseases
tolerated the injected dosage well. Severe side effects were uncommon.
1.3.2 Active-Targeted Imaging
Active targeting is expected to improve upon the passive targeting approach and
increase the specificity of cellular uptake. Active targeting is achieved by conjuga-
tion of anti-receptor molecules to the nanoparticle surface. Binding then induces
prolonged interaction of nanoparticles with cancer cell surfaces and results in
elevated cellular uptake. The targeting ligand selected for the nanoparticles could
be a peptide, protein and its derivatives, an aptamer, or a small molecule like folate.
This strategy has been studied extensively and is being expanded as new surface
receptors for different cancer types are identified. Different cancer types such as
breast cancer, glioblastoma, ovarian cancer, liver cancers and so on have been
imaged using the targeted imaging method [ 4 ]. Even though studied extensively in
in vitro laboratory situations, application in clinical studies can be impeded due to
the additional synthetic and purification steps. A select group of reports on targeted
imaging are now discussed to better familiarize the readers with this approach.
In one study Weissleder and coworkers were able to show that it is possible to
image transgene expression in vivo by MRI using an active-targeted imaging
method [ 32 ]. The group studied an engineered transferrin receptor (ETR)
expressing cell line (ETR positive) and ETR negative gliosarcoma cells. They
were able to show that the ETR positive cells tended to take up the probe 500 %
more efficiently in cell culture than ETR negative cells. The nanoparticles used for
this study were dextran coated superparamagnetic nanoparticles conjugated to
human holo-transferrin proteins, which specifically target transferrin. The group
implanted ETR positive and negative cells to the right and left flank of nude mice,
respectively. After the tumors developed, the probe was injected and imaged by
T2-weighted MRI. The MRI results demonstrated that the nanoparticles preferen-
tially accumulated in ETR positive tumors.
In another study Moore and coworkers used synthetic peptides conjugated to
iron oxide nanoparticles to image adenocarcinoma cells in vivo [ 23 ]. The cellular
target in this study was the underglycosylated mucin-1 (uMUC-1) antigen, which is
a transmembrane molecule overexpressed by most human epithelial cancer cells.
A synthetic peptide EPPT was conjugated to the nanoparticles covalently as a