MEDICAL DEVICE INNOVATION - Medical Device Daily

MEDICAL DEVICE INNOVATION 2010
Gold-wrapped nanotubes may be
formula for better imaging
By LYNN YOFFEE
Medical Device Daily Staff Writer
A thin layer of gold wrapped around nanotubes may be
the secret formula for a better contrast imaging agent – one
that enhances absorption of laser radiation and simultaneously
reduces toxicity. This new imaging agent being
developed at the University of Arkansas and
University of Arkansas for Medical Sciences (UAMS;
Little Rock) is capable of molecular mapping of lymphatic
endothelial cells and detecting cancer metastasis in sentinel
lymph nodes.
“The absorption of near-infrared (NIR) radiation is an
important issue for non-invasive photoacoustic [laserinduced
sound wave] detection and photothermal [laserinduced
heat] treatment,” Jin-Woo Kim, associate professor
in the department of biological and agricultural engineering
at the University of Arkansas, told Medical Device Daily.
“Indeed, because most biotissues are relatively transparent
to NIR radiation, targeting of tumor cells with strongly NIR
absorbing nanoparticles could allow both highly sensitive
diagnosis and targeted killing of tumors noninvasively in a
whole body at the laser energy, which is safe for surrounding
healthy tissue.”
Many researchers have avoided using nanotubes as
part of imaging agents because of the potential toxicity
that comes with these little hollow particles. But Kim and
his collaborator, Vladimir Zharov, professor in the Winthrop
P. Rockefeller Cancer Institute at UAMS, found that gold
solved the problem and even enhanced the effectiveness of
radiation. The gold nanotubes required low laser-energy
levels for detection and low concentrations were required
for effective diagnostic and therapeutic applications.
Their work – which targeted imaging lymphatic vessels
in mice – is reported in the current issue of Nature
Nanotechnology.
In a previous study, Kim and Zharov demonstrated that
carbon nanotubes held a great promise as NIR contrast
agents for photoacoustic detection and photothermal
killing of individual bacteria in the blood system. However,
they suffer from relatively poor NIR absorption, and questions
abound about their toxicity.
“We addressed this problem by depositing a thin layer
of gold around the carbon nanotubes. The gold layer
enhanced absorption of laser radiation and reduced toxicity,”
Kim said. “In vitro tests showed only minimal toxicity
associated with the golden carbon nanotubes (GNTs).
Furthermore the synthesis process is very robust and simple,
inexpensive and environmentally friendly green one.
The reaction of the carbon nanotubes and gold chloride
occurs in water and happens at ambient temperature. No
other chemicals or special conditions, such as heating, are
135
required.”
The team’s GNTs synthesized in this study are shorter
than carbon nanotubes used in the previous study, but they
absorb NIR radiation at least twice as effectively.
“Two-order higher concentrations of carbon nanotubes
will be required to have the same photothermal responsiveness
as GNTs,” Kim said. “Taking into account the issue
of toxicity – i.e., as long as the controversy exists and until
full-scale studies prove one way or the other, we should not
assume the particles to be safe. The amount of nanoparticles
applied for biomedical applications, such as in vivo
clinical diagnosis in human, becomes more important. The
less, the better. Furthermore, gold is chemically inert, so it
is highly possible to rule out potential toxicity.”
Kim said that recently gold-based nanoparticles, in particular
gold nanoshells AuroLase, made by Nanospectra
Biosciences (Houston) and colloidal gold nanospheres conjugated
with tumor necrosis factor alpha, made by
Cytimmune Sciences (Rockville, Maryland), have been
approved for pilot clinical trials for cancer treatments. That
led his team to assume a gold coating could potentially
improve the biocompatibility of carbon nanotubes.
Some of the unique features of GNTs compared with
existing nanoparticles include:
• One of the highest near-infrared absorption at a
minuscule diameter (up to 3 nm-5 nm).
• Absorption can be adjusted in NIR window of transparency
of biotissue to provide deeper laser penetration
and advanced diagnosis.
• They provide multimodal function as triple contrast
agents for photoacoustic and photothermal detection and
photothermal therapy.
“With the GNT with such unique property, we successfully
demonstrated in vivo molecular mapping of lymphatic
vessels, and targeted detection and purging of metastasis
in lymph nodes, which is an important site of tumor
spreading,” Kim said. “This new nanomaterial could be an
effective alternative to existing nanoparticles and fluorescent
labels for non-invasive targeted imaging of molecular
structures in vivo.”
In addition to diagnosing cancer, Kim said the GNTs
could also be used therapeutically for cancer as well as bacterial
and viral infections, such as antibiotic-resistant
staphylococcus aureus.
“For example, in this study, we demonstrated molecular
detection of lymphatic endothelial cells and highly precise
targeted destruction of lymphatic wall in vivo,” he said.
“This holds promise for mapping and destruction of intraor
peri-tumor lymph vessels that provide initial dissemination
of detached tumor cells to metastatic sites. Another
example is to apply our developed technique for the detection
and purging of cancer metastasis in so-called sentinel
lymph nodes that is important for early cancer staging with
potential to improve cancer treatment and reducing
patient’s morbidity through replacement of conventional
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