Summary: Researchers have created an implantable, multi-layered nanofiber treatment for aggressive brain tumors that delivers a combination of three approved drugs directly to the surgical site. The NanoMesh system embeds temozolomide, acriflavine, and PT2385 in a layered electrospun fiber scaffold to produce a synergistic therapeutic effect, overcome the blood-brain barrier, and provide both immediate and extended drug release. In animal experiments the approach markedly extended survival and produced long-term survivors.
By bypassing systemic delivery limitations and releasing drugs locally at the tumor margin after surgery, the NanoMesh reduces the ability of glioblastoma cells to adapt and escape single-agent therapies. This targeted strategy minimizes systemic exposure while sustaining therapeutic concentrations at the site where recurrence is most likely.
Key Facts
- Targeting a difficult cancer: Glioblastoma is the most common and aggressive primary brain tumor in adults. Its intra-tumoral heterogeneity allows rapid adaptation and resistance to single-agent treatments, so multidimensional strategies are necessary to shut down multiple escape routes simultaneously.
- Pharmaceutical synergism: The NanoMesh co-delivers three FDA-approved agents—temozolomide, acriflavine, and PT2385—that act on complementary pathways. In combination these agents produce synergistic cytotoxicity in glioma cells, meaning their joint effect exceeds the sum of each drug used alone.
- Local delivery and the blood-brain barrier: Systemic chemotherapy is often limited by the blood-brain barrier. The NanoMesh is implanted at the resection cavity, delivering drugs directly into brain tissue. In this configuration the barrier helps contain therapeutics locally, protecting the rest of the body from off-target toxicity.
- Electrospun nanofiber engineering: The NanoMesh is manufactured by electrospinning, an electric-field process that forms controlled, multilayer fiber membranes. This method allows precise tuning of implant geometry, layer composition, drug loading, and release kinetics to match clinical needs.
- Strong preclinical results: In animal models of glioblastoma, untreated subjects died rapidly (within about 15–19 days). Animals treated with the three-layer NanoMesh lived substantially longer—on average about twice as long—and 40% of treated animals survived beyond the 120-day endpoint, remaining disease-free for an extended plateau.
- Translational potential: The collaborative team from the University of Cincinnati and Johns Hopkins Medicine is optimizing long-term release profiles and nanofiber architectures with the aim of developing a clinically translatable implantable platform for glioblastoma and other hard-to-treat cancers.
Source: University of Cincinnati
Overview: Investigators at the University of Cincinnati and Johns Hopkins Medicine designed a nanofiber implant that embeds three distinct cancer drugs into separate layers of a polymer mesh. The mesh is placed at the tumor resection site so that it delivers a controlled burst of medication followed by sustained local release, concentrating therapy where residual tumor cells remain and reducing systemic side effects.
Lead author Daewoo Han and UC Distinguished Research Professor Andrew Steckl incorporated temozolomide, acriflavine, and PT2385 into coaxial electrospun fiber membranes to create the NanoMesh. Steckl’s NanoLab specializes in precise electrospinning methods that produce tailored, multilayer fiber scaffolds for localized drug delivery.
Steckl emphasized the power of the drug combination: when paired inside the NanoMesh the agents interact synergistically to produce a notably stronger anti-tumor response than each drug alone. This synergism helped prevent tumor cells from exploiting alternate survival pathways.
The research team published these findings in the journal ACS Biomaterials Science & Engineering. The project received support from the National Institutes of Health. Co-authors include neurosurgery specialists and translational researchers from Johns Hopkins who are focused on multimodal approaches to improve outcomes for patients with recurrent and treatment-resistant brain tumors.
Glioblastoma’s tendency to recur is tied to its cellular diversity and ability to mutate under therapeutic pressure. The NanoMesh approach seeks to limit that adaptability by delivering multiple agents at effective local concentrations and maintaining exposure over time, reducing the window for resistant clones to emerge.
In preclinical tests the implant’s structural control allowed researchers to fine-tune drug release profiles and implant geometry. The blood-brain barrier, typically a barrier to systemic chemotherapy, becomes an advantage when therapies are delivered locally—trapping drugs where needed and shielding the rest of the body from toxicity.
Researchers are continuing to optimize multi-layer nanofiber designs to extend and control release patterns, with the expressed goal of advancing to clinical trials. If successfully translated, this platform could offer a new localized therapeutic option for patients with glioblastoma and other difficult-to-treat cancers.
Key Questions Answered:
A: Glioblastoma contains highly diverse cell populations that can rapidly mutate in response to single-agent treatments. Combined with the protective blood-brain barrier that limits systemic drug penetration, these factors make it hard to deliver effective, sustained therapy to tumor cells without significant side effects.
A: NanoMesh uses electrospinning to form a multilayer nanofiber patch. Each layer encapsulates a distinct drug formulation and is engineered to release its payload on a specific schedule, producing an initial high-concentration dose followed by prolonged, lower-rate release directly at the resection margin.
A: Synergism occurs when combined drugs produce a greater effect than the sum of their individual effects. In this study, the three-drug combination confined within the NanoMesh limited tumor escape mechanisms and produced substantial survival benefits, including long-term survival in a subset of treated animals.
Editorial Notes:
- This article was edited by a neuroscience news editor.
- The full journal paper was reviewed by the editorial team.
- Additional context was added by staff to clarify experimental details and translational goals.
About this neurotech and brain cancer research news
Author: Michael Miller
Source: University of Cincinnati
Contact: Michael Miller – University of Cincinnati
Image credit: 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 remains a highly aggressive brain tumor with limited improvement in long-term outcomes. This study reports a coaxial electrospun fiber membrane (NanoMesh) embedding temozolomide and inhibitors of hypoxia-inducible factors (acriflavine, PT2385). In vitro assays identified synergistic drug combinations across glioma cell lines. Preliminary animal studies with three-drug-loaded NanoMesh showed a median survival improvement of more than 50 days and a long-term survival rate of 40% beyond 120 days, supporting the potential of this platform as a translatable local therapy for glioblastoma.