Summary: Researchers developed a highly advanced, implantable brain cancer treatment that uses multi-layered drug-embedded nanofibers to eliminate aggressive tumors. The research details a breakthrough “NanoMesh” drug delivery system that administers three federally approved cancer drugs in a state of pharmaceutical synergism.
By bypassing the restrictive blood-brain barrier and deploying both immediate and long-lasting doses directly to the tumor site post-surgery, this localized technology successfully prevents cancer cells from mutating or pivoting, dramatically extending survival rates in animal models.
Key Facts
- The Multi-Dimensional Assault: Adult glioblastoma is the most common and aggressive form of brain cancer, notoriously difficult to treat because its highly heterogeneous cell layout allows it to rapidly mutate and evade single-drug therapies. To prevent the cancer from pivoting, researchers developed a multi-dimensional treatment strategy that attacks the tumor from several molecular angles simultaneously.
- The Power of Pharmaceutical Synergism: Investigators discovered that combining three federally approved glioblastoma medications, temozolomide, acriflavine, and PT2385, triggers a phenomenon known as synergism. Working in concert, the combined drugs prove vastly more effective at destroying cancer cells than when any of the compounds are administered alone.
- Bypassing the Blood-Brain Barrier: Traditional systemic chemotherapies are heavily restricted by the blood-brain barrier, which blocks toxic medicines from entering the brain from the bloodstream. The NanoMesh resolves this by delivering medicine locally. Paradoxically, this barrier works in the patient’s favor during localized therapy, acting as a structural shield that traps the medicine in the brain and protects the rest of the body from toxic chemotherapy side effects.
- Electrospun Nanofiber Engineering: Developed in Professor Andrew Steckl’s NanoLab at UC alongside lead author Dr. Daewoo Han, the delivery system relies on an electric field to create an intricate, electrospun fiber membrane. This process builds a customized, multi-layered mesh that gives clinicians total structural control over implant geometry, precise medication dosage, and long-term release timing.
- Doubled Survival Rates in Animal Trials: The therapeutic efficacy of the tri-drug NanoMesh was validated during animal testing. While 100% of the untreated glioblastoma models died within 15 to 19 days, the majority of the mice treated with the multi-layered nanofiber patch survived twice as long. Strikingly, 40% of the treated mice completely outlived the 120-day experiment, maintaining a survival plateau that stretched for over 80 days.
- A Translatable Future for Complex Cancers: Co-author Professor Betty Tyler of Johns Hopkins underscores that while current frontline therapies have successfully extended patient survival, this localized nanofiber architecture offers a superior alternative. The collaborative team is actively optimizing advanced nanofiber structures to manage long-term drug release, with the ultimate goal of translating the system into human clinical trials for glioblastoma and other hard-to-treat cancers.
Source: University of Cincinnati
Researchers with the University of Cincinnati and Johns Hopkins Medicine developed a potential treatment for brain cancer that uses nanofibers embedded with a combination of drugs that work in concert to target tumors.
The drugs proved more effective in combination than when administered alone and can provide both immediate and long-lasting doses to kill cancer cells.
Lead author Daewoo Han, an assistant professor in UC’s College of Engineering and Applied Science, and UC Distinguished Research Professor Andrew Steckl incorporated the drugs into electrospun fiber membranes, creating a nanofiber drug delivery system. Steckl’s NanoLab at the University of Cincinnati is a leading developer of this technology that uses an electric field to create a multilayered fiber mesh for drug delivery, among other uses.
“This combination is pretty powerful,” Steckl said.
Glioblastoma is the most common and aggressive form of brain cancer in adults. Researchers at UC and Johns Hopkins found that the three federally approved drugs used to treat glioblastoma (temozolomide, acriflavine and PT2385) work better in combination than they would alone, a pharmaceutical phenomenon called synergism.
“When you add them together, three things can happen,” Steckl said. “The combination is negative; the effect is additive, like one plus one equals two; or it’s synergistic, which is like one plus one equals three.”
The study was published in the journal ACS Biomaterials Science & Engineering. The research was supported with a grant from the National Institutes of Health.
Steckl said glioblastoma is extremely difficult to treat because its heterogeneous cells allow for mutations that help the cancer evade treatment.
“It’s tough to control,” Steckl said. “It comes in through the window and when you close the window, it comes through the door. And when you close that, it comes through the chimney.”
Glioblastoma also has high recurrence. And the blood-brain barrier limits the effectiveness of other traditional chemotherapies.
“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,” UC’s Han said.
UC researchers worked with a team at Johns Hopkins Medicine, including Betty Tyler, a professor of neurosurgery, and postdoctoral researcher Hasan Slika. Tyler said researchers are looking to attack the disease with combinations of therapies.
“Unfortunately, cancers know how to pivot to evade therapeutic treatment,” she said. “So we’re approaching treatment multidimensionally.”
Tyler has helped develop other cutting-edge therapies now commonly used to treat cancer.
“Current therapies have increased patient survival and given them more birthdays,” she said. “But we’re still working on improving options.”
In animal trials, all untreated mice with glioblastoma died within 19 days. But a majority of mice treated with the three-layer nanofiber mesh survived twice as long. And 40% survived past the 120-day conclusion of the experiment in a plateau that stretched for more than 80 days.
Han said using electrospun fiber mesh, doctors can precisely control the dosage and release and the implant geometry, which contribute to its effectiveness. And just as the blood-brain barrier protects the brain from toxins, the barrier also protects the body from the toxic side effects of the medicine applied to the brain, Han said.
UC researchers are now working on optimizing the long-term release of medicines using advanced nanofiber structures. And the delivery system has broad potential in applications for other difficult-to-treat diseases, Han said.
“What’s next will be very exciting,” Han said. “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.”
Key Questions Answered:
A: Because it acts as a master of evasion. Glioblastoma tumors are made up of incredibly diverse, mixed cell types that can rapidly mutate the moment they encounter a single cancer drug. As the researchers describe it, if you close the window on this cancer, it simply slips through the door or down the chimney. Combined with the blood-brain barrier blocking standard chemotherapies from reaching the brain, treating it has historically been an uphill battle.
A: Through an advanced manufacturing process called electrospinning. Scientists use an electric field to weave a highly specialized, multi-layered mesh out of tiny nanofibers. This allows engineers to trap three distinct, federally approved drugs inside separate layers of the patch. Once implanted at the surgical site, the mesh safely dictates the release timing, providing an immediate heavy punch followed by a slow, continuous trickle of medicine directly to the remaining tumor cells.
A: Synergism is a biological phenomenon where multiple drugs work together to create an effect far greater than the sum of their individual parts. Instead of an additive effect like 1 + 1 = 2, synergism behaves like 1 + 1 = 3. By combining temozolomide, acriflavine, and PT2385 inside the NanoMesh, the drugs locked down the tumor’s escape routes. This team-up allowed 40% of the treated animal subjects to survive completely past the 120-day mark of the experiment in a stable, healthy plateau.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this neurotech and brain cancer research news
Author: Michael Miller
Source: University of Cincinnati
Contact: Michael Miller – University of Cincinnati
Image: The image is credited to Joseph Fuqua II
Original Research: Open access.
“Codelivery Material System of Polymer Microfiber Structures for Synergistic Localized Therapy of Glioblastoma” by Daewoo Han, Hasan Slika, Aanya Shahani, Eliana S. Wolf, Charles G. Eberhart, Henry Brem, Betty Tyler, and Andrew J. Steckl. ACS Biomaterials Science & Engineering
DOI:10.1021/acsbiomaterials.5c01482
Abstract
Codelivery Material System of Polymer Microfiber Structures for Synergistic Localized Therapy of Glioblastoma
Glioblastoma is a highly aggressive brain tumor whose treatment has improved little over the past decade. We report on the synergistic effect of the FDA-approved anti-GBM drug (temozolomide) and inhibitors (acriflavine, PT2385) of hypoxia-inducible factors (HIFs) embedded into coaxial fiber membranes (NanoMesh). In vitro cytotoxicity has been evaluated for various glioma cell lines, and synergistic drug combinations have been identified.
Preliminary animal studies with the three-drug-loaded NanoMesh indicate a significant improvement of median survival of >50 days and long-term (>120 days) survival rate of 40%, indicating the potential of this material platform as a translatable local GBM therapy.
