One factor that makes glioblastoma cancers so difficult to treat is that malignant cells from the tumours spread throughout the brain by following nerve fibers and blood vessels to invade new locations. Now, researchers have learned to hijack this migratory mechanism, turning it against the cancer by using a film of nanofibers thinner than human hair to lure tumours away.
Instead of invading new areas, the migrating cells latch onto the speciallydesigned nanofibers and follow them to a location - potentially outside the brain - where they can be captured and killed. Using this technique, they can partially move tumours from inoperable locations to more accessible ones.
Though it won't eliminate the cancer, the new technique reduced the size of brain tumours in animal models, suggesting that this cancer might one day be treated more like a chronic disease.
"We have designed a polymer thin film nanofiber that mimics the structure of nerves and blood vessels that brain tumour cells normally use to invade other parts of the brain," explained Ravi Bellamkonda, lead investigator.
"The cancer cells normally latch onto these natural structures and ride them like a monorail to other parts of the brain. By providing an attractive alternative fiber, we can efficiently move the tumours along a different path to a destination that we choose."
Researchers from Georgia Tech report the details of the technique in the journal Nature Materials.
Treating the Glioblastoma multiforme cancer (GBM), is difficult because the aggressive and invasive cancer often develops in parts of the brain where surgeons are reluctant to operate. Even if the primary tumour can be removed, however, it has often spread to other locations before being diagnosed.
New drugs are being developed to attack GBM, but the Atlanta-based researchers decided to take a more engineering approach. Anjana Jain, who is the first author of the study. As a Georgia Tech student, Jain worked on biomaterials for spinal cord regeneration.
Then later in the Bellamkonda lab, she applied her work to develop potential new treatment modalities for GBM. "The signaling pathways we were trying to activate to repair the spinal cord were the same pathways researchers would like to inactivate for glioblastomas," said Jain. "Moving into cancer applications was a natural progression, one that held great interest because of the human toll of the disease."
Tumours typically invade healthy tissue by secreting enzymes that allow the invasion to take place. That activity requires a significant amount of energy from the cancer cells. "Our idea was to give the tumour 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 to expend any energy," she explained. The researchers created fibers made from polycaprolactone (PCL) polymer surrounded by a polyurethane carrier.
The fibers, whose surface simulates the contours of nerves and blood vessels that the cancer cells normally follow, were implanted into the brains of rats in which a human tumour was growing.
The fibers, just half the diameter of a human hair, served as tumour guides, leading the migrating cells to a "tumour collector" gel containing the drug cyclopamine, which is toxic to cancer cells. For comparison, the researchers also implanted fibers containing no PCL or an untextured PCL film in other rat brains, and left some rats untreated.
The tumour collector gel was located physically outside the brain.
After 18 days, they found that compared to other rats, tumour sizes were substantially reduced in animals that had received the PCL nanofiber implants near the tumours. Tumour cells had moved the entire length of all fibers into the collector gel outside the brain. While eradicating a cancer would always be the ideal treatment, Bellamkonda said, the new technique might be able to control the growth of inoperable cancers, allowing patients to live normal lives despite the disease.
Instead of invading new areas, the migrating cells latch onto the speciallydesigned nanofibers and follow them to a location - potentially outside the brain - where they can be captured and killed. Using this technique, they can partially move tumours from inoperable locations to more accessible ones.
Though it won't eliminate the cancer, the new technique reduced the size of brain tumours in animal models, suggesting that this cancer might one day be treated more like a chronic disease.
"We have designed a polymer thin film nanofiber that mimics the structure of nerves and blood vessels that brain tumour cells normally use to invade other parts of the brain," explained Ravi Bellamkonda, lead investigator.
"The cancer cells normally latch onto these natural structures and ride them like a monorail to other parts of the brain. By providing an attractive alternative fiber, we can efficiently move the tumours along a different path to a destination that we choose."
Researchers from Georgia Tech report the details of the technique in the journal Nature Materials.
Treating the Glioblastoma multiforme cancer (GBM), is difficult because the aggressive and invasive cancer often develops in parts of the brain where surgeons are reluctant to operate. Even if the primary tumour can be removed, however, it has often spread to other locations before being diagnosed.
New drugs are being developed to attack GBM, but the Atlanta-based researchers decided to take a more engineering approach. Anjana Jain, who is the first author of the study. As a Georgia Tech student, Jain worked on biomaterials for spinal cord regeneration.
Then later in the Bellamkonda lab, she applied her work to develop potential new treatment modalities for GBM. "The signaling pathways we were trying to activate to repair the spinal cord were the same pathways researchers would like to inactivate for glioblastomas," said Jain. "Moving into cancer applications was a natural progression, one that held great interest because of the human toll of the disease."
Tumours typically invade healthy tissue by secreting enzymes that allow the invasion to take place. That activity requires a significant amount of energy from the cancer cells. "Our idea was to give the tumour 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 to expend any energy," she explained. The researchers created fibers made from polycaprolactone (PCL) polymer surrounded by a polyurethane carrier.
The fibers, whose surface simulates the contours of nerves and blood vessels that the cancer cells normally follow, were implanted into the brains of rats in which a human tumour was growing.
The fibers, just half the diameter of a human hair, served as tumour guides, leading the migrating cells to a "tumour collector" gel containing the drug cyclopamine, which is toxic to cancer cells. For comparison, the researchers also implanted fibers containing no PCL or an untextured PCL film in other rat brains, and left some rats untreated.
The tumour collector gel was located physically outside the brain.
After 18 days, they found that compared to other rats, tumour sizes were substantially reduced in animals that had received the PCL nanofiber implants near the tumours. Tumour cells had moved the entire length of all fibers into the collector gel outside the brain. While eradicating a cancer would always be the ideal treatment, Bellamkonda said, the new technique might be able to control the growth of inoperable cancers, allowing patients to live normal lives despite the disease.
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