A new technique could offer a targeted approach to fighting cancer: low-intensity pulses of ultrasound have been shown to selectively kill cancer cells while leaving normal cells unharmed.
Associate Professor and Director of Music at Skidmore College, Anthony Holland, tells the audience that he has a dream. That dream is to see a future where children no longer have to suffer from the effects of toxic cancer drugs or radiation treatment, and today he and his team believe they have found the answer, and that answer is sound.
Holland and his team wondered if they could affect a cell by sending a specific electric signal, much like we do with LCD technology. After searching the patent database for a device that could accomplish this, they came across a therapeutic device invented by New Mexico physician Dr. James Bare. The device uses a plasma antenna that pulses on and off, which, as Holland explains, is important because a constant pulse of electricity would produce too much heat and therefore destroy the cell. For the next 15 months, Holland and his team searched for the exact frequency that would directly shatter a living microorganism. The magic number finally came in the form of two inputs, one high frequency and one low.
The high frequency had to be exactly eleven times higher than the low, which in music is known as the 11th harmonic. At the 11th harmonic, micro organisms begin to shatter like crystal glass.
After consistently practicing until they became efficient at the procedure, Holland began working with a team of cancer researchers in an attempt to destroy targeted cancer cells. First they looked at pancreatic cancer cells, eventually discovering these cells were specifically vulnerable between 100,000 – 300,000 Hz.
In repeated and controlled experiments, the frequencies, known as oscillating pulsed electric field (OPEF) technology, killed an average of 25% to 40% of leukaemia cells, going as high as 60% in some cases. Furthermore, the intervention even slowed cancer cell growth rates up to 65%.
It spares healthy cells while taking out cancerous ones
Most cancer treatments involve surgery, chemical poisons or toxic radiation. Because they tend to take out healthy cells along with cancerous ones, these treatments can leave patients tired, hurting and more. So researchers are looking for new approaches that spare the healthy cells. One new idea would destroy cancer cells with ultrasound energy. Even this treatment, however, can sometimes damage healthy tissue. But a new development may help. It limits the ultrasound energy’s damage to only the cancer cells. Healthy cells should suffer little if any harm from it.
It’s exciting, says David Mittelstein of his team’s findings. Mittelstein is a biomedical engineer at the California Institute of Technology, in Pasadena. Low-intensity ultrasound, he says, “may allow physicians to target cancer cells based on their unique physical and structural properties.” Any spillover of the energy should cause little harm to healthy tissue.
The treatment sends out pulses of sound waves — energy — that have a frequency above 20,000 hertz (cycles per second). That’s too high for our ears to hear. (That’s also what makes it “ultra” sound.) Medical imaging relies on very short pulses of this low-intensity ultrasound.
Doctors had already used high-intensity ultrasound to kill cancer cells. These sound waves send lots of energy to a small, focused area. The waves vibrate water inside cells within that area. This causes the cells to heat up. A lot. Targeted cells and their neighbors can reach 65° Celsius (149° Fahrenheit) in just 20 seconds. This kills cancer cells. The down side: It kills healthy ones, too.
Mittelstein’s team wanted to try something different.
Another Caltech lab had studied effects of low-intensity ultrasound on cancer cells. These cells differ from healthy ones. They have a bigger nucleus. They’re softer, too. This other Caltech team created computer models of cancer cells. These models suggested that low-intensity ultrasound might kill those cells. The process, Mittelstein explains, is “similar to how a trained singer can shatter a wine glass by singing a specific note.”
This idea hadn’t been tested, however. So his team set out to do that.
First, they mixed cancer cells with healthy blood cells and immune cells. The cells were all suspended in a liquid. Then the scientists directed short pulses of low-intensity ultrasound at this suspension.
The team tested different ultrasound frequencies (ranging from 300,000 to 650,000 hertz). They also tested different pulse durations (from 2 to 40 milliseconds). One minute of 500,000 hertz ultrasound, delivered in 20-millisecond bursts, killed nearly every cancer cell. It didn’t hurt the blood cells. It also left more than eight in every 10 immune cells unharmed. Mittelstein rates it a huge success.
A role for microbubbles
The treatment caused super-small microbubbles — likely tiny bubbles of air present in the fluid — to merge. The ultrasound waves caused these bigger bubbles to oscillate (move back and forth). The oscillation caused these microbubbles to grow, then violently collapse. To kill cancer cells, Mittlestein reports, “microbubble oscillation was necessary — but not sufficient.” Microbubbles oscillated in both healthy and cancer cells. “But only the cancer cells,” he notes, “were vulnerable to certain frequencies of ultrasound.”
More damage occurred when the ultrasound waves bounced back to hit the cancer cells more than once.
The initial ultrasound waves are known as traveling waves. They move out from the machine that produces them. But when those waves hit a surface of some type, they can reflect back — into the oncoming traveling waves. The colliding waves combine to form a special pattern known as “a standing wave,” Mittelstein notes. And this wave has some “special stationary spots called ‘nodes,’” he explains. At these, the pressure remains constant. Some other stationary spots, called “anti-nodes,” also develop. In them, he says, “the pressure goes up and down at twice the amplitude [height] of the traveling wave.” In the end, bubbles in the standing wave oscillate more than do those in a normal wave. And that extra oscillation proved essential to killing cancer cells.
The team suspects the standing wave brings microbubbles closer together. That then boosts the ultrasound energy deposited on the cells, Mittelstein says. Not all cells respond equally to this standing wave. Which do will depend on their physical properties. Here, only cancer cells were harmed.
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