Scientists have recently determined that gold nanorods and other
nanostructures can be used to target and destroy tumor cells, but it
was generally assumed that cell death was due to the high heat
produced by the light-absorbing nanoparticles. The Purdue team
discovered, however, that a more complex biochemical scenario is
responsible for killing the cells.
"We have found that rather than cooking the cells to death, the
nanorods first punch holes in the membrane, and cell death is then
chemically induced, in this case by an influx of calcium," said
Alexander Wei, an associate professor of chemistry at Purdue.
Findings are detailed in a research paper appearing Oct. 19 in the
journal Advanced Materials. The paper, which appeared online last
week, was written by doctoral students Ling Tong, Yan Zhao, Terry B.
Huff and Matthew N. Hansen, along with Wei and Cheng.
The gold rods are less than 15 nanometers wide and 50 nanometers long,
or roughly 200 times smaller than a red blood cell. Their small size
is critical for the technology's potential medical applications: the
human immune system quickly clears away particles larger than 100
nanometers, whereas smaller nanoparticles can remain in the
bloodstream far longer.
Shining light on the gold nanorods causes them to become extremely
hot, ionizing the molecules around them.
"This generates a plasma bubble that lasts for about a microsecond, in
a process known as cavitation," Wei said. "Every cavitation event is
like a tiny bomb. Then suddenly, you have a gaping hole where the
nanorod was."
The gold nanorods also are ideal for a type of optical imaging known
as two-photon luminescence, used by Cheng and his research group to
monitor the position of nanorods in real time during tumor-cell
targeting. The imaging technique provides higher contrast and brighter
images than conventional fluorescent imaging methods.
In experiments with tumor cells in laboratory cultures, the nanorods
attached to the cell membranes and were eventually taken up into the
cells. The researchers found that it could take far less power to
injure cells by exposing the nanorods to near-infrared light while
they are still on the membrane surface instead of waiting until the
nanorods are internalized.
"This means that if you wait until the nanorods are inside the cell,
then you really have to pump up the laser power, so localizing the
nanorods on the cell membrane strongly influences their ability to
inflict cell damage," Cheng said.
The findings suggest an optimal window of opportunity for applying
near-infrared light to the nanorods for cancer treatment.
"We like to believe this opens the possibility of using nanorods for
biomedical imaging as well as for therapeutic purposes," Cheng said.
The Purdue researchers observed that light-absorbing nanorods cause
the formation of membrane "blebs, " similar to severe blistering.
These blisters, however, are not produced directly by the high heat
generated by the nanorods.
"The blebbing is triggered by the nanorods, but it's really caused
through a complex biochemical pathway - a chemically induced process,"
Cheng said. "Extra calcium gets into the cell and triggers enzyme
activity, which causes the infrastructure inside the cell to become
loose, and that gives rise to the membrane blebs."
Researchers used a calcium-sensitive fluorescent dye to back up their
argument that calcium influx caused the tumor cell death. When the
nanorod-bearing tumor cells were maintained in a calcium-free nutrient
medium, no blisters were formed if the nanorods were exposed to
near-infrared light. But when the researchers added calcium to the
medium, the blebbing took place immediately.
Although the technique offers promise for a new cancer treatment, it
is too early to determine when it could be in clinical use, said Wei,
who is collaborating with the National Cancer Institute to determine
the suitability of the functionalized gold nanorods for future
clinical studies.
The research has been supported by the National Science Foundation and
the National Institutes of Health. The research also has been
supported by Purdue's Oncological Sciences Center and the Purdue
Cancer Center.
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