Biomedical Engineering Reference
In-Depth Information
accommodate multiple small ligands that enable multivalent targeting to one or
more biomarkers, new designs are emerging which allow increased target affin-
ity for individual probes. Molecular specific modified NMs have more detailed
ability to provide specific information that is not possible using conventional
methods.
The most simple possible application of targeted NMs in nanopharmacol-
ogy is the intravenous injection of contrast agent that could be used to non-
invasively detect the expression of biomarkers that are important for disease
diagnosis and the treatment selection, eliminating the need for invasive biopsy.
The design of many of the new nanoparticle-based contrast agents in preclini-
cal testing today are designed with this principle as a goal aside from improved
biocompatibility, long circulation times, less repeat administration of contrast,
dynamic monitoring of biomarker expression behavior and levels with time and
medication, all of which are essential for determining disease progression and
response to therapy.
3
Smarter NMs designed for probing disease states and progression through
the collection of important information from specific molecular targets before,
during, and after treatment may further revolutionize the current state of medi-
cine. For example, elevated telomerase activity is associated with poor prog-
nosis and increased risk of recurrence of cancer.
292
Such capabilities coupled
with the knowledge about other prognostic proteins or nucleotide levels could
be used for a more informed decision on the selection of personalized therapy.
The use of multimodal nanoparticles that can be used for delivery of multiple
agents as well as be detected in multiple ways can find essential information
about disease state and treatment efficacy simultaneously. This is shown by the
new NMs designed by Xie et al.
276
which contains both AuNP and Fe
3
O
4
. The
AuNP can be used for X-ray contrast while the Fe
3
O
4
can be used in magnetic
imaging modality. In addition, the Cy5.5 label is a very sensitive dye for NIR
fluorescence in the FANPs. The NIR fluorescence is quenched until the cleav-
age of the Leu-Gly bond releases the Cy5.5 containing fragments which exhibit
the signal.
The group of Pandey and coworkers
293
investigated the possibility of deliv-
ering contrast agents to living tumor cells by conjugating gadolinium complexes
to hexylether derivative of pyropheophorbide, HPPH, a tumor-avid chlorophyll
derivative at Phase II clinical trials. Up to six Gd
3+
aminobenzyl DTPA com-
plexes were coupled to HPPH that had enhanced tumor-imaging potential,
which increased with a larger number of Gd
3+
units. The three Gd
+ 3
aminoben-
zyl DTPA conjugates that showed the best PDT activity in vitro showed higher
accumulation in the tumor at 24 h post-injection
293
compared with that in blood,
muscle, and most organs.
A lot of research has come up in the areas where multifunctional NMs are
used as a combination of detection and therapeutic functions. This integration
that is called “theranostics” is attractive because it allows the imaging detection
of therapeutic delivery and at the same time performs informed observation
