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Tuesday, October 16, 2007

Laser activate Gold nanorods trigger complex biochemical mechanism to kill cancer

Researchers have shown how tiny "nanorods" of gold can be triggered by a laser beam to blast holes in the membranes of tumor cells, setting in motion a complex biochemical mechanism that leads to a tumor cell's self-destruction.

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.

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.