UA project tackles spread of cancer cells
Magnetic capture in findings
Saturday, November 28, 2009
FAYETTEVILLE — Researchers at the state's medical school and its land-grant university have discovered a way to magnetically trap tumor cells circulating in the bloodstream.
Their finding, published Nov. 15 in the journal Nature Nanotechnology, might ultimately stop cancer's deadly metastasis and improve early diagnosis of the disease in its various forms.
A team led by Vladimir Zharov of the University of Arkansas for Medical Sciences worked with Jin-Woo Kim,a biomedical engineering researcher at the University of Arkansas at Fayetteville, on the project.
Metastasis occurs when cancer cells break away from their original tumor site and spread to other parts of the body.
The researchers describe their technique as an intravenous injection of a "cocktail" of magnetic and gold-covered carbon nanotubes containing a special biological coating into the bloodstream to target the moving cancer cells.
An ordinary magnet at-tached to the skin near the injection site would then attract and capture the cells.
Then, two ways of removal are envisioned: The trapped tumor cells could be microsurgically taken from blood vessels and genetically analyzed, or eradicated directly in the vessels by non-invasive laser irradiation performed through the skin.
Kim's main contribution to the technique is the golden nanotubes, which Zharov credited with boosting the technique's sensitivity, or ability to catch more bad cells.
The project is funded through a four-year, $1.2 million grant from the National Institutes of Health's National Cancer Institute that began in July, Zharov said.
Taking only a standard blood sample risks missing cancer cells in the earliest stages of metastasis, Kim said while working in his lab Wednesday afternoon. Yet screening all the blood in the body, which typically contains 5 liters' worth, would take a long time.
That's where the magnetic capture comes in.
The new method's use of magnetic collection of cells from blood circulating throughout the entire body - using the magnet on the outside of the body and the magnetic nanoparticles and Kim's golden nanotubes in the blood - has the potential to increase capture of the tumor cells by up to 1,000 times compared with existing technology.
"We ultimately want to have single-cell detection," Kim said. "In the biomedical field, it's about early detection. If we have to waittill 100 cells are present in the system, it might be too late."
The researchers attribute most cancer deaths to the metastasis of cancer cells from a primary tumor to other parts of the body via the bloodstream.
NANOTECHNOLOGY DEFINED
"Nano," derived from the Greek word for "dwarf," is a prefix meaning one-billionth.
In the nanosciences, researchers in disciplines such as engineering, physics, chemistry, biology or computer technology study materials at the molecular or atomic scale.
Separately, or in projects that cross disciplines, the scientists explore how the particles self-assemble or respond to manipulation in hopes of designing superior medicines, chemicals, fuels, electronic devices, medical techniques or other inventions. Thus nanotechnology is an approach rather than a discipline.
It is the second time since August that Zharov and Kim were featured in Nature Nanotechnology.
Four months ago, the journal reported the two had developed a technique to perform molecular mapping of lymphatic endothelial cells and detect cancer metastasis in lymph nodes closer to a primary tumor.
In May, Zharov also spoke of other, similar research projects.
In one, he is working with scientists at the University of Little Rock's Nanotechnology Center on a method of locating and killing cancer cells in the bloodstream. In the other, he and a team of 10 researchers were working on a non-invasive technique that hunts circulating cancercells using naturally occurring nanoparticles within the cells themselves.
NEAR-INFRARED LIGHT
Kim said the gold in his gold-covered carbon nanotubes is relatively low in toxicity compared with other substances, noting that gold has been used in fillings and other medical applications in the human body for years.
The golden tubes respond efficiently and effectively to the laser irradiation technique.
"My part of the project is developing the particles and characterizing how they respond to the laser," he said. "We don't want our nanotubes attaching to good cells - just the bad cells." Biological coatings, in this case antibodies, allow the nanotubes to recognize and capture the tumor cells.
"My gold nanotubes respond well to near-infrared light," Kim said, which is the point on the light spectrum where the laser is the safest for use on human tissue. Using that kind of light, "Our body doesn't heat up, but the particle heats up." That allows for detection.
The detection is where Zharov comes in.
"We use laser to generate sound from different cells," Zharov said in his pronounced Russian accent. "It's called photo-acoustic effect."
When the particles heat up, they vibrate, and Zharov finds them through the sound waves they emit.
"Dr. Zharov's part is the photo-thermal and photoacoustic technique," Kim said. "He's a world leader in applying both technologies to biological images and therapy."
The photo-thermal method uses heat for detection, but the photo-acoustic method is better for "imaging purposes," Kim said.
COULD APPLY TO INFECTIONS
The project that was published Nov. 15 could have a number of applications.
"It's relatively universal procedure, applicable for all kinds of cancer," Zharov said. Scientists adapt the technique from, say, breast cancer to skin cancer by changing the biological coating on the nanoparticles to a different cancer-specific protein.
UAMS officials said the discovery using magnetics and the gold nanotubes garnered Zharov and his team a mention in Faculty of 1000 Biology, a Web site that showcases papers of interest published in the biological sciences that are then nominated by the world's top researchers.
The most recent project and related cancer-cell targeting projects could potentially have applications for targeting bacteria and viruses as well, the researchers said.
YEARS OF TESTING AHEAD
It likely would take awhile before the scientists could bring an actual application to market, as further testing must be done.
The researchers have gained permission from a UAMS protocol committee for pre-clinical studies that would examine the safety of the procedure, Zharov said. Such studies usually involve mice or "ex vivo" examination - meaning test-tube scrutiny of the human patients' blood.
Clinical trials in humans would have to be done later.
"Under optimistic prognosis, it would take about two, three years in our plans," Zharov said.
Northwest Arkansas, Pages 9 on 11/28/2009
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