Nanofiber 'monorails' ferry brain tumors to their death

Date: Feb-18-2014Glioblastoma is the deadliest form of brain cancer, and one reason it is difficult to

treat is because tumor cells spread to other parts of the brain by following nerve fibers and

blood vessels. Now, using nanofiber "monorails," biomedical engineers have found a way to

hijack this migratory feature and lure the malignant cells elsewhere.

The idea is to entice the migrating cancer cells toward a more accessible location where they

can be killed. This could be outside the brain, for instance.

Another option, for example, could be to move tumors from inoperable locations to somewhere

surgeons can remove them more easily.

While it is unlikely such a method will remove the cancer completely, the hope is one day a

deadly disease may be transformed into one that is treated more like a chronic one.

When they tested the method in animals, the researchers found it reduced the size of brain

tumors.

They report their work in the journal Nature Materials.

Each year in the US, around 10,000 people are diagnosed with glioblastoma. They are currently

treated with chemotherapy, radiation and surgery, but even when they receive all three, patients

rarely live more than 18 months after diagnosis.

Cancer cells latch onto man-made nanofibers and 'ride them like a monorail'

Nanofibers are so-called because they are extremely thin, in this case, about half the

thickness of human hair, and on a scale compatible with nerve fibers and blood vessels. Lead

researcher Ravi Bellamkonda, professor and chair of the Wallace H. Coulter Department of

Biomedical Engineering at Georgia Tech and Emory University in Atlanta, explains:

"We have designed a polymer thin film nanofiber that mimics the structure of nerves and blood

vessels that brain tumor cells normally use to invade other parts of the brain."

"The cancer cells normally latch onto these natural structures and ride them like a monorail

to other parts of the brain," he continues. "By providing an attractive alternative fiber, we

can efficiently move the tumors along a different path to a destination that we choose."

He adds that an attractive feature of such a method could be that it offers an alternative to drug

and radiation treatments:

"There are no drugs entering the blood stream and circulating in the brain to harm healthy

cells. Treating these cancers with minimally-invasive films could be a lot less dangerous than

deploying pharmaceutical chemicals."

Enticing tumor cells down a path of least resistance

The team had the idea of using nanofibers to treat glioblastoma because of work that had

already been done on making biomaterials to repair spinal cord injuries. There are similarities

in the work, for example the signaling pathways involved are the same.

Tumor cells usually invade healthy tissue by secreting enzymes to prepare the way. The cells

have to spend a lot of energy to make this happen. The researchers thought if they could offer the

cells a migration route where they did not have to spend a lot of energy, they would take

it.

First author Anjana Jain, assistant professor in the Department of Biomedical Engineering at

Worcester Polytechnic Institute in Massachusetts, who worked on the study when she was a

postdoctoral fellow in the Bellamkonda lab, says:

"Our idea was to give the tumor cells a path of least resistance, one that resembles the

natural structures in the brain, but is attractive because it does not require the cancer cells

to expend any more energy."

For the study, the team made nanofibers from polycaprolactone (PCL) polymer surrounded by a

polyurethane carrier. The surface of the material is very simular to the contours of blood

vessels and nerve fibers that the tumor cells travel along.

The researchers implanted the nanofibers into the brains of rats that had human

glioblastomas.

The team also treated other groups of rats for comparison. These were implanted with

nanofibers that had no PCL, or were made from untextured PCL film, or were untreated.

Treated rats showed significant glioblastoma tumor shrinkage

The tumor cells migrated along the nanofibers to a tumor collector outside the brain. The

tumor collector contained a gel with the drug cyclopamine, which is toxic to cancer cells.

After 18 days, the results showed that the rats treated with PCL nanofiber implants near the

tumors showed significant reductions in tumor sizes. Plus, their tumor cells had migrated along

the entire length of all nanofibers into the collector gel.

Prof. Bellamkonda says that while eradicating cancer would be ideal, an approach based on the

method they demonstrated might at least offer a way to control the growth of inoperable cancers,

and give patients a chance to live normal lives.

"Perhaps with ideas like this, we may be able to live with cancer just as we live with

diabetes or high blood pressure," he adds.

It will be some time before the technique moves from the lab into the clinic, maybe 10 years

or more, says the team.

Next steps include seeing how the method might work with other types of brain cancer and

cancers that are difficult to remove.

Funds from the National Cancer Institute of the National Institutes of Health (NIH) helped

finance the study.

Meanwhile, Medical News Today recently reported how researchers in Canada reactivated immune cells to treat

brain cancer. After treating diseased mice with a drug that reactivated immune cells that

are deactivated in glioblastoma, the animals lived two to three times longer.

Written by Catharine Paddock PhD




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