Researchers have developed a nanofiber implant that delivers a triple combination of drugs directly to the site of the most aggressive form of brain cancer, extending survival in animal studies and offering new hope for patients with glioblastoma. In experiments, 40 percent of treated mice survived beyond 120 days, while all untreated animals died within 19 days.
The new approach uses an electrospun fiber mesh, called NanoMesh, that is embedded with three federally approved drugs: temozolomide, acriflavine and PT2385. Scientists at the University of Cincinnati and Johns Hopkins Medicine found that when used together, the drugs produce a synergistic effect, meaning their combined impact is greater than the sum of their individual effects. “When you add them together, the combination can be negative, additive, or synergistic. This is like one plus one equals three,” said lead author Daewoo Han, an assistant professor at UC’s College of Engineering and Applied Science.
Glioblastoma is the most common and deadly form of brain cancer in adults. It is notoriously difficult to treat because its cells mutate rapidly to evade therapy. The blood brain barrier also blocks many standard chemotherapy drugs from reaching the tumor. The NanoMesh system is designed to be placed directly at the tumor site after surgery, releasing precise doses of medication both immediately and over a long period. “It’s tough to control. It comes in through the window and when you close the window, it comes through the door,” said UC Distinguished Research Professor Andrew Steckl, describing the cancer’s evasiveness. “Our NanoMesh system was designed to solve these issues by enabling localized long term delivery of multiple synergistic drugs directly at the tumor site after surgery,” Han added.
Researchers say the implant also minimizes side effects because the blood brain barrier keeps the drugs contained within the brain, protecting the rest of the body from toxicity. In animal trials, a majority of mice treated with the three layer nanofiber mesh survived twice as long as untreated mice, and 40 percent lived past the experiment’s 120 day endpoint. “Unfortunately, cancers know how to pivot to evade therapeutic treatment. So we’re approaching treatment multidimensionally,” said Betty Tyler, a professor of neurosurgery at Johns Hopkins Medicine who helped develop other widely used cancer therapies.
The team is now working to optimize the long term release of medicines using advanced nanofiber structures. Han noted the delivery system could also be adapted for other difficult to treat diseases. “What’s next will be very exciting. Our ultimate goal is moving forward to a clinically translatable system that improves both survival and quality of life for patients with difficult to treat cancers, including glioblastoma,” he said.