Biomedical Engineering Reference
In-Depth Information
Overall, the results of the study showed that the new nanoparticles system created
has the following features: specifi c tumor homing; an avoidance of the RES; and
the provision of effective tumor imaging. Although the binding of CREKA- SPIO
to tumor vessels does not require clotting activity, the clotting does improve the
effi ciency of the tumor homing and enhances the tumor signal in whole-body
scans.
Leuschner
et al.
[164] utilized SPIONs for targeted delivery to metastatic cancer
cells in peripheral tissues, lymph nodes and bones to enhance the sensitivity of
MRI. Up to 60% of human breast cancers express receptors for luteinizing
hormone/chorionic gonadotropin ( LH/CG ) and luteinizing hormone - releasing
hormone (LHRH) [165-168]. In this study, SPIONs were linked to LHRH, with
LH/CG-bound SPIONs being developed to test their ability to accumulate in
LHRH-expressing human breast cancer cells, both
in vitro
and
in vivo
. When
particles were incubated with MDA-MB-435S luc cells, the highest iron accumula-
tion was 452.6 pg Fe per cell for LHRH-SPIONs, 203.6 pg Fe per cell for beta-CG-
SPIONs, and 51.3 pg Fe per cell for SPIONs. Similarly,
in vivo
in a nude mouse
model, LHRH-SPIONs were specifi cally targeted and accumulated into tumors
and metastatic cells of human breast cancer xenografts. The amount of LHRH-
SPIONs in the lungs was directly dependent on the number of metastatic cells,
and amounted to 77.8 pg Fe per metastatic cell. In contrast, unconjugated SPIONs
accumulated in the liver, showed a poor affi nity to the tumor, and were not detect-
able in metastatic lesions in the lungs. LHRH-SPIONs accumulated in the cyto-
solic compartment of the target cells and formed clusters, but did not accumulate
in the livers of normal mice. Thus, the study results provided another contrast
agent for MRI
in vivo
and demonstrated an increased sensitivity for the detection
of metastases and disseminated cells in lymph nodes, bones, and peripheral
organs.
During recent years, many reports have been made of
in vivo
gene silencing by
short interfering RNAs ( siRNA s) [169 - 172] . In this connection, RNA interference
(RNAi) has emerged as one of the promising strategies in the development of
therapeutics, and dual-purpose probes have been developed for the detection of
siRNA delivery and silencing of genes by novel noninvasive methods [173]. In
order to develop these probes, MNPs were effectively used as nanoplatforms for
the dual imaging and delivery of siRNA therapeutics. The probes were capable of
the
in vivo
transfer of siRNA and the simultaneous imaging of its accumulation
in tumors, both by MRI and near- infrared
in vivo
optical imaging (NIRF).The
reported multifunctional MNPs were tagged with a near-infrared dye and cova-
lently linked to siRNA molecules that were specifi c for model or therapeutic
targets. Additionally, these nanoparticles were modifi ed with a membrane trans-
location peptide for intracellular delivery. An
in vivo
tracking of tumor uptake of
these probes by MRI and optical imaging in two separate tumor models was
established. This study represented the fi rst step towards an advancement of the
siRNA delivery and imaging strategies that are essential for cancer therapeutic
product development and optimization, utilizing MNPs as a multifunctional plat-
form [173] .
