Glioblastoma multiforme is an aggressive, invasive brain tumor with a poor survival rate. Available treatments are ineffective and some tumors remain inoperable because of their size or location. The tumors are known to invade and migrate along white matter tracts and blood vessels. A team of scientists now exploit this characteristic of glioblastoma multiforme by engineering aligned polycaprolactone (PCL)-based nanofibers for tumor cells to invade and, hence, guide cells away from the primary tumor site to an extracortical location. This extracortical sink is a cyclopaminedrug-conjugated, collagen-based hydrogel. When aligned PCL-nanofibre films in a PCL/polyurethane carrier conduit were inserted in the vicinity of an intracortical human U87MG glioblastoma xenograft, a significant number of human glioblastoma cells migrated along the aligned nanofiber films and underwent apoptosis in the extracortical hydrogel. Tumor volume in the brain was significantly lower following insertion of aligned nanofiber implants compared with the application of smooth fibers or no implants.
Using this technique, researchers can partially move tumors from inoperable locations to more accessible ones. Though it won’t eliminate the cancer, the new technique reduced the size of brain tumors in animal models, suggesting that this form of brain 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 tumor cells normally use to invade other parts of the brain,” explained Ravi Bellamkonda, lead investigator and chair of the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. “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 tumors along a different path to a destination that we choose.”
Tumor cells typically invade healthy tissue by secreting enzymes that allow the invasion to take place, she explained. That activity requires a significant amount of energy from the cancer cells. “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,” she explained.
- Anjana Jain et al., Guiding intracortical brain tumour cells to an extracortical cytotoxic hydrogel using aligned polymeric nanofibres, Nature Materials, 2014, DOI: 10.1038/nmat3878