Biomedical Engineering Reference
In-Depth Information
(Toledo) [65]. For imaging, these aptamers were bound to three spectrally different
fl uorophore - doped silica nanoparticles (cy5 - doped, Rubpy - doped, and TMR - doped
nanoparticles).
Chen
et al.
showed that aptamers conjugated to magnetic and fl uorescent
nanoparticles could be effectively employed to extract and enrich small cell lung
cancer (SCLC) cells from whole blood (spiked with SCLC cells), and to detect SCLC
cells in sections of formalin- fi xed paraffi n - embedded SCLC and non - small cell
lung cancer (NSCLC) cells [66]. This cell-based SELEX strategy involved generating
DNA aptamers (71-base single-stranded DNA) that were specifi c for molecular
markers on SCLC cells but did not cross-react with normal epithelial cells nor
NSCLC cells; the result was fewer false positives and a greater selectivity. This
approach could represent a tremendous advantage over the use of antibodies,
which may cross-react with atypical epithelial cells and not have suffi cient specifi c-
ity. As noted above, this method also has the potential for enriching rare CTCs
from peripheral blood for analysis.
5.9
Conclusions
Today, magnetic nanoparticles of novel and various formulations are being devel-
oped for the improved
in vivo
and
in vitro
diagnosis of cancer. Areas of focus for
magnetic nanoparticle research and development have included improved biocom-
patibility, optimization of specifi c targeting, enhanced
in vivo
imaging, and novel
signal detection and measurement platforms for molecular diagnostics. In particu-
lar, the use of magnetic nanoparticles as both MRI contrast agents and nanocar-
riers has attracted enormous attention, as they hold tremendous promise as
multifunctional agents that can perform imaging, drug delivery, and real-time
monitoring simultaneously. Bioengineers and chemists are making great advances
in the synthesis of new metal/alloy composite nanoparticle cores to enhance their
magnetic properties. They are also exploring novel nanomaterials for surface
coating to improve the biocompatibility and biosafety of magnetic nanoparticles.
One critical component of the bench-to-bedside translation of these advances for
magnetic nanoparticle-based therapy is the continued investigation into relation-
ships between the physico-chemical properties of the nanostructures and their
behavior
in vivo
, which is currently poorly understood. Hence, a greater insight
into the mechanisms that dictate the fate of nanoparticles
in vivo
is required.
In the case of magnetic nanoparticle-based
in vitro
diagnostics, one major chal-
lenge in the translation of these platforms - for which proof - of - concept has been
demonstrated in simple test solutions of analytes, or by using common biomarkers
found in great abundance - is to determine whether their performance holds up
in clinical samples and for low-expression cancer biomarkers that are meaningful
for diagnosis, prognosis, and a prediction of response to therapy. As research
groups begin to consider moving their assay systems forward, beyond the proof-
of-concept stage, a variety of factors related to assay performance must be consid-
