(Note: This article was corrected on 12/9/09 – previously, it said that the nanoparticles were activated by UV light, but the TiO2 particles are actually modified to be activated using normal, visible light. Also, the light exposure time was only 5 minutes, not 6 hours as previously reported in the text.)
As reported everywhere today, Sen. Ted Kennedy died Tuesday night after a year-plus fight with malignant glioma, a type of brain cancer. The condition, in which tumor cells arise from glia cells of the brain, is known to be especially deadly and hard to treat – only about 16 percent of patients diagnosed with the condition survive five years. Treatment involves radiation, surgery and chemotherapy, but long-term survival is a challenge.
“In some cancers, the brain or pancreatic cells are multiplying at such a rapid rate,” said Dr. Maciej Lesniak, director of neurosurgical oncology at the University of Chicago Brain Tumor Center. “When you have a cancer that grows that rapidly, the prognosis can usually be measured in months or years at most. It’s always a battle between how quickly the cancer is growing and the available therapies.”
Those grim numbers have inspired many researchers to look at improved ways of treating brain tumors, employing some of the latest technologies available in biomedicine. One promising tool, currently being tested by Lesniak and scientists at Argonne National Laboratory, is the use of nanomaterials to target and kill tumor cells with minimal damage to nearby healthy tissue. A laboratory demonstration of this method was published last month in the journal Nano Letters.
“This paper overcomes a potential challenge in nanomedicine,” Lesniak said. “While nanotechnology is very interesting in terms of applications, targeting nanoparticles to specific parts of the body is a problem. They are so small, they can go anywhere.”
First, a public service announcement for those confused by the flood of nano-news: “nano” only means really, really small. The nanometer is a unit of measurement that equals one-billionth of a meter; you’d need 10 million nanometer-long objects to get from 0 to 1 cm on your ruler. So nanotechnology is simply the design and use of very, very tiny objects in fields like electronics and medicine.
In this case, the nanoparticle being tested as a potential cancer treatment is titanium dioxide, an unusual compound currently used for everything from treating wastewater to self-cleaning windows to movie snow. The special thing about titanium dioxide (or TiO2 in chemistry shorthand) is that it’s a photocatalyst – expose it to light and it generates free radicals, unstable atoms, that can destroy dirt on a window or, potentially, kill off a cell.
The problem for the latter use is how to get TiO2 into the cells you want to kill, the ones in the tumor, without taking out a lot of innocent bystanders along the way. Argonne researchers solved this issue by attaching titanium dioxide to an antibody for the interleukin receptor, a molecule expressed on the cell surface of tumor cells. Essentially, the antibody in this case is a key that only works in certain locks (the interleukin receptor), and when it finds the right cell, it is brought inside along with its TiO2 party guest.
At first, that TiO2 doesn’t cause any trouble – it’s kind of a sleeper agent inside the tumor cell. But when the cell is exposed to light, it begins producing free radicals, which wreak havoc with the cell’s internal organs and cause it to self-destruct.
Experiments conducted by the research team at Argonne proved that this set-up could work, at least in the artificial environment of the laboratory. The modified TiO2 trojan horses successfully attached themselves to cancer cells that were grown in the lab, and even to the “invadopodia” of those cells – tendrils used by cancer cells to attack neighboring cells. When these cells were exposed to light for 5 minutes, 80% of the tumor cells died off after 6 hours.
“When exposed to light, these nanoparticles actually cause the death of cancer cells,” Lesniak said. “There are many scenarios where this could work. For example, during surgery while resecting a tumor, you could inject these nanoparticles, target the tumor and expose it to a source of light.”
However, about 15% of normal cells were also bound by TiO2 particles and died after light exposure, collateral damage that Lesniak said would be a potential concern, though it’s comparable to side effects of existing treatments.
“You have to offset against the certainty of death when you’re dealing with this kind of aggressive cancer,” he said.
The tests, while encouraging, are also miles of research away from clinical application. The next step, already underway, is to test the method in animal models. Only then can clinical trials begin, and if successful, full implementation would still be years in the future. That’s too late for Sen. Kennedy (who, among many other accomplishments, was lauded today for his support of cancer research), but may someday help malignant glioma sufferers receive a more hopeful prognosis.
“It’s so early in this one yet; one should be cautious but optimistic,” Lesniak said.