Biomedical Engineering Reference
In-Depth Information
[127]. The endocytosed particles were not targeted to the Golgi apparatus for recy-
cling, but rather accumulated within the lysosomes. In T
1
- weighted MR images,
signal enhancement owing to the magnetic particles was greater for cells with
magnetic particles bound to the cell surface than for cells that internalized the
particles. These fi ndings indicated that the targeting of prostate cancer cells using
PSMA offered a specifi c and sensitive technique for the enhancement of MR
images [127] .
6.3.3.2
Antibody Fragment - Directed MNP s
A single - chain Fv ( scFv ) gene which was specifi c to
- seminoprotein was developed
for the treatment of prostate cancer; the ScFv antibody fragments were subse-
quently linked with MNPs for molecular-targeting in prostate cancer therapy or
diagnosis, as reported by Han
et al.
[128]. In this case, the human seminoprotein
secreted by the prostate tumor provides a specifi c antigen [129]. In this study, the
ScFv were used to deliver MNPs into prostate cancer cells for imaging the tumors.
The results also showed that ScFv specifi c for seminoprotein were able to bind
prostate cells specifi cally, and to transport the magnetic beads rapidly (within
15 min) into the tumor cells. The quantity of magnetic beads located inside the
tumor was increased as the culture time was prolonged. ScFv- conjugated magnetic
beads did not enter non- specifi c control cells [128]. Antibody scFv fragments were
also used by Natarajan
et al.
[130], who linked the MNPs to anti MUC-1 di-scFv
by site - specifi c coupling methods to target breast cancer cells for the focused
hyperthermia created within them by an alternating magnetic fi eld ( AMF ). In this
preparation, MNPs were attached to di - scFv - cysteine at a well - defi ned site. Studies
with whole-body auto radiography (Figure 6.6a) and pharmacokinetic investiga-
tions (Figure 6.6b) showed the di-scFv-directed MNPs to be effectively targeted in
breast cancer cells in mice [130] .
Lee
et al.
[131] developed engineered iron oxide nanoparticles (MEIO) and
MnMEIO to target cancer and to provide ultra-sensitive MRI. In particular, molec-
ular probes based on MnMEIO have strong magnetic properties, demonstrated a
considerably enhanced sensitivity for cancer cell detection, and also permitted
imaging of the smallest possible tumors
in vivo
. MnMEIO nanoparticles were also
conjugated to the cancer-targeting Herceptin antibody [132, 133], which binds
specifi cally to the HER2/neu marker that is overexpressed in breast and ovarian
cancers [134] . Both, MnMEIO - and MnMEIO - Herceptin proved to be biologically
nontoxic. When these particles were compared to the CLIO- Herceptin conjugates
[135] for their cancer cell-detecting ability, FACS analyses indicated that almost
identical numbers of MnMEIO and CLIO nanoparticles were bound to cancer
cells.
In these studies, MnMEIO-Herceptin conjugates (200 ml) were administered
(
n
= 8, dose 20 mg kg
−1
) to nude mice implanted with NIH3T6.7 cells in the proxi-
mal femur region, and MR images subsequently obtained before and at 1 and 2 h
after injection. The color-coded MR images shown in Figure 6.7a-c indicated that
the tumor site had been targeted and well detected. When the same experiment
was performed with CLIO-Herceptin conjugates at the same dose level, no
γ
