Gold-coated nanotubes used as imaging agent to detect tumour cells
11 September 2009
Researchers at the University of Arkansas and University of Arkansas
for Medical Sciences have developed a special contrast-imaging agent
that is capable of molecular mapping of lymphatic endothelial cells and
detecting cancer metastasis in sentinel lymph nodes.
The new material could be used as a more efficient and less toxic
alternative to nanoparticles and fluorescent labels used in the
non-invasive, targeted molecular detection of normal cells, such as
immune-related cells, and abnormal cells, such as cancer cells and
bacteria. Findings were published in Nature Nanotechnology.
Research teams led by Jin-Woo Kim, associate professor in the
department of biological and agricultural engineering at the University
of Arkansas, and Vladimir P. Zharov, professor in the Winthrop P.
Rockefeller Cancer Institute at UAMS, worked with carbon nanotubes and
gold. In a previous study, Kim and Zharov demonstrated that carbon
nanotubes held great promise as contrast agents for photoacoustic
detection and photothermal killing of individual bacteria in blood
Developed by Zharov, photoacoustic and photothermal methods deliver
energy, via laser pulses, into biological tissue. When some of the
energy is absorbed and converted into heat, it expands and emits sound
waves. However, the carbon nanotubes had not been fully developed as an
imaging agent because of concerns about toxicity.
Kim’s research team 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. In vitro tests showed only
minimal toxicity associated with the golden nanotubes. Compared to
existing nanoparticles, the golden nanotubes also exhibited high laser
absorption at a miniscule diameter. The golden nanotubes required
extremely low laser-energy levels for detection, and low concentrations
were required for effective diagnostic and therapeutic applications.
The synthesis process is simple, inexpensive and environmentally
friendly, Kim said. 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 required.
In the recent study, the golden nanotubes were used as contrast
agents with the advanced imaging methods. The researchers applied the
golden nanotubes to solve the challenging biomedical problem of
detecting cancer cells in the lymphatic system, which is responsible for
the process of metastasis.
Specifically, the researchers coupled the golden nanotubes with an
antibody specific to a critical lymphatic-endothelial receptor. This
enabled the mapping of lymphatic endothelial cells, which line the
internal surface of lymphatic vessels. This is important because
lymphatic endothelial cells come into direct contact with other cells,
such as immune-related cells, tumor cells and bacteria entering the
lymphatic system. The specific receptor, known as LYVE-1, is one of the
most widely used markers of lymphatic endothelium.
Zharov, Ekaterina Galanzha, research assistant professor at UAMS, and
other colleagues on Zharov’s team successfully demonstrated the unique
ability of the golden nanotubes for integrated diagnosis and therapy at
the single cell level. This included targeted lymphatic mapping and the
eradiation of cancer micro-metastasis in the critical sentinel lymph
nodes, the first lymph node or group of nodes reached by metastasizing
cancer cells from a primary tumor.
The large surface area on the golden nanotubes may allow
bioconjugation, or cooperation, with several biomarkers targeted
simultaneously. Absorption can be adjusted for multi-color targeting
because the size of the nanotubes can be changed easily by modulating
the length and diameter of nanotube core and thickness of the gold
layer, Kim said. This advantage may increase the percentage of
detectable cells within a targeted cell population and may allow
multiple targets to be detected simultaneously. Also, the golden
nanotubes’ hollow core could carry therapeutic agents, such as drugs,
magnetic materials, ethanol and other chemicals, to further enhance
their therapeutic effects.
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