Iron Oxide Nanoparticles and Derivatives for Biomedical Imaging and Application in Cancer Diagnosis and Therapy - Bioanalysis Advanced Materials Methods and Devices - page 6

targeting ligand, which was derived from a monoclonal antibody (ASM2) raised
against human epithelial cancer cells. The peptide showed a remarkable affinity for
uMUC-1. The nanoparticles were further conjugated to a near infrared dye (cy5.5)
to gather additional information about tumor specific accumulation by in vivo
optical imaging. The authors tested several uMUC-1 positive human cancer cells
from different organs in order to gather broader information about interaction
between the conjugated nanoparticles and the transmembrane molecule including
nanoparticle uptake both in vitro and in vivo. In vitro cell binding assays indicated
that the uMUC-1 positive cells had a greater nanoparticle uptake (attributed to the
interaction with EPPT). In vivo, mice were implanted with uMUC-1 positive and
negative tumor cells in the right and left flanks to evaluate and compare the probe
uptake by several different human adenocarcinomas. The results showed that
indeed the uMUC-1 positive cells tended to take up the probe to a greater extent
than the antigen-negative cells. These results were confirmed by in vivo magnetic
resonance and optical imaging.
In another study Kumar et al. showed that myristoylated polyarginine peptide
(MPAP)-functionalized iron oxide nanoparticles showed a significant uptake by
orthotopically implanted gliomas in mice [ 16 ]. Gliomas are very aggressive and
progress very quickly. Detection of brain cancer at early stages of development is
important to fight the disease. In this study, the authors were able to specifically
target U-87 human glioma cells and identify each tumor using in vivo MRI. In this
type of brain tumor the blood brain barrier becomes leaky and has pores as large as
100 nm. Exploiting the leakiness of the vasculature and utilizing a cationic mem-
brane translocation peptide (MPAP), a significant nanoparticle passage was
achieved into the tumor interstitium and then into the tumor cells.
1.3.3 Magnetic Relaxation Switching
Magnetic Relaxation Switching (MRS) is an event where the magnetization effi-
cacy of nanoparticles changes as their state of dispersity changes. When iron oxide
nanoparticles aggregate they become more efficient at changing the T2 relaxation
time of the neighboring protons and when they go from an aggregated to a dispersed
state they return back to their initial magnetization. This property of magnetic
nanoparticles has been used to detect several target molecules via magnetic relaxa-
tion switching. The target could be a physiologically relevant material such as a
virus, protein, metal ions or other indicators of biological events [ 25 , 36 ].
In one study, telomerase activity in malignant cells was investigated by MRS
[ 9 ]. Telomerase activity is elevated in many malignancies and is believed to play a
significant role in tumorigenesis. Detection of telomerase activity is important in
following cancer development, designing telomerase inhibitors, adjusting treatment
dosage, and understanding enzymatic functions and levels. The authors designed
magnetic nanoparticles that bind to telomerase-associated repeat units (TTAGGG),
forming small clusters of assembled magnetic nanoparticles depending upon the