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Microscopic particles have huge possibilites
Imagine all the parts that make up a car. Dozens of different pieces work together to create a functioning machine, and it is only when all of these parts operate at once that the machine works. Now imagine this type of sophistication working at a small enough level to fit inside a blood cell.
Nanotechnology, which involves the use of extremely small materials, has begun to play a role in the treatment of cancer. While nanoparticles have been used for a few years in magnetic resonance imaging (MRI) technology to help detect certain cancers in their early stages, their potential as treatment is currently being explored in laboratories around the world.
Andrew Maynard, chief science advisor to the Project on Emerging Nanotechnologies at the Woodrow Wilson Center in Washington, D.C., explained that nanotechnology works on a scale almost as small as atoms, the smallest component of a substance. A nanometer is one billionth of a meter.
When working on this scale, Maynard said a whole new range of possibilities for treatments develop, such as more specific targeting abilities for drug therapy.
“Now, we very crudely flood the body with toxins in the hope they kill the tumor before they kill the person,” Maynard said.
The goal of nanotechnology with cancer is to localize treatment instead of forcing the entire body to deal with chemicals that can harm healthy cells. The hope is to engineer drugs that can be delivered by nanoparticles that seek out and destroy only cancer cells. Think of making a machine rather than a chemical, Maynard said.
“You’re creating particles that can do many things,” he said. “It’s not a passive chemical, it’s an active device.”
There are three aspects to nanotechnology that fascinate most people, Maynard said. The first is “smallness” because of how much scientists are learning to do at such a small scale. The second is “strangeness,” because of how odd some materials behave on a nano scale. Gold is an example of this.
At its normal size, the mineral is gold in color and chemically motionless; this is why we are able to wear it as jewelry. However, at very small sizes, gold becomes red and is very chemically active, Maynard said. It is one of the most common materials used in nanotechnology.
“Many materials behave very strangely at such small scales,” he said. “We can tap into these strange properties.”
The third aspect is the sophistication involved in the technology. Scientists have known about atoms for decades but have not been able to work on that scale because they did not have the technology to do so.
“Imagine trying to make fine jewelry with thick gloves on; that’s what scientists have felt like,” Maynard said. “Now the gloves have come off.”
There are many different materials used in nanotechnology, targeting different kinds of treatment opportunities. Gayle Woloschak, a professor and radiobiologist for the Robert E. Lurie Comprehensive Cancer Center at the Feinberg School of Medicine at Northwestern University, said the goal is to create multi-functioning nanoparticles that can release chemotherapy drugs, target the cancer agent and image it.
“The hope is to use nanodevices to enter cells and cause manipulations,” Woloshack said.
She works with a team that is using titanium dioxide on a scale of about six nanometers. At that size, different particles can be made to bind to its surface, she explained. The titanium dioxide can be used to carry out a charge transfer, and while Woloschak said the process is one that not even most chemists fully understand, the anticipated result is to be able to cut cancer DNA out of an infected cell.
In lab cultures as well as animal studies, Woloschak said they have been able to target cancer cells and image them with MRI, but scientists are just starting to test the nanoparticle as a therapy. She and her colleagues are working with Papilloma viruses, such as the Human Papilloma Virus that has been linked to cervical cancer.
“We’re pretty optimistic about it,” she said.
As with any new experimental treatment, there are concerns. Woloschak said because the particles are so small, they should be able to clear the kidney and pass out of the body, but some particles may remain. Potential consequences to having the particles stay in the body are unknown.
“Whenever you’re putting something new in a person, you’re worried about what the side effects can be,” she said.
Unlike other materials being explored for use, such as cadmium, titanium dioxide is not known to produce toxicity. There is an iron oxide nanoparticle used for cancer imaging with MRI that was approved by the Food and Drug Administration and has been in use for several years.
“I think a lot of work needs to be done to show it’s safe … [but] I think most of those limitations can be overcome,” Woloschak said.
George Whitesides, professor of chemistry and chemical biology at Harvard University, said that while the technology sounds impressive, he thinks the focus should be on using nanoparticles in imaging and diagnosing, not treatment.
The problem lies in being able to deliver the treatment to the right cells, and Whitesides said this has proven difficult.
“Cancer cells are abnormal cells, but they’re still us,” he said.
The nanoparticles sent in to destroy the cancer cells may also destroy unaffected cells, because they can sometimes have cancer markers even if they’re healthy. Tumors have also been known to be “genetically flexible” and mutate around several different therapies, Whitesides explained. This keeps them from getting recognized by the therapeutic drugs.
The other problem with targeting cancer cells is the likelihood that only large tumors will be targeted, missing smaller clumps of developing tumors.
“We need something that finds isolated [cancer] clumps that’s somewhere else in the tissue … it’s not a tumor, it’s a whole bunch of tumors,” Whitesides said.
The upside to the treatment possibilities is that they buy the patient time, he said, which is very important to many cancer patients.
“It’s easy to say that one is going to have a particle that’s going to recognize the tumor once it gets there and will do something that triggers the death of the cell, it’s just that we don’t know how to do either one of these parts,” he said.
There is no simple solution. The more scientists learn about biology the more complicated it becomes, not less. Whitesides said one effective way to deal with cancer is to reduce the risk of getting it by reducing the environmental factors that lead to cancer.
“It’s a biology problem, not a particle problem,” he said.
With the creation of vaccines against certain cancers, earlier diagnoses, better imaging techniques and progressively better treatments, we are chipping away at the problem.
“Nanotechnology is like any other technology,” Maynard said. “We just want to make sure we’re asking the right questions to get the right answers.”