A self-assembling peptide nanofiber was engineered to co-deliver a glycolysis inhibitor and a chemotherapy drug specifically to glioblastoma cells, crossing the blood-brain barrier and showing enhanced tumor-killing effects.
2 drugs, 1 nanofiberCo-delivery of 3-bromopyruvate and temozolomide via a single peptide-based platform with BBB-penetrating and tumor-targeting capabilities
What the researchers found
The peptide nanofiber successfully co-delivered 3-bromopyruvate (a glycolysis inhibitor) and temozolomide (a standard chemotherapy drug) to glioblastoma cells. The system used an MMP-9-responsive linker for controlled, on-demand drug release at the tumor site. The nanofiber was functionalized with the falGea peptide for EGFRvIII-targeted delivery and gH625 for blood-brain barrier penetration.
In both 2D and 3D U-87 MG glioblastoma cell cultures, the combination therapy delivered via the nanofiber platform demonstrated therapeutic efficacy. Testing with a dynamic 3D in vitro blood-brain barrier model confirmed that the gH625 peptide enhanced transport across the BBB.
Why it matters
Glioblastoma is one of the most aggressive and difficult-to-treat brain cancers, partly because the blood-brain barrier blocks most drugs from reaching the tumor. This peptide-based delivery system addresses two major challenges at once: getting drugs across the BBB and combining two complementary therapies to attack cancer through different pathways, potentially reducing the doses needed and limiting side effects.
How the study worked
The researchers designed a self-assembling peptide nanofiber and characterized its aggregation behavior, structural stability, and shape. They tested its effects on isolated rat brain mitochondria to confirm mitochondrial targeting. Anti-cancer activity was evaluated in U-87 MG glioblastoma cells grown in both traditional flat cultures (2D) and more realistic spheroid cultures (3D). Blood-brain barrier permeability was tested using a dynamic 3D in vitro BBB model.
What this study cannot tell us
This study was conducted entirely in laboratory settings — using cell cultures and an in vitro BBB model, not living animals or human patients. While the 3D culture and BBB models are more realistic than basic cell tests, they still don't capture the full complexity of a living brain tumor environment. The long-term stability, toxicity profile, and actual in vivo efficacy of the nanofiber system remain to be determined.
How to read the evidence
This is a preclinical laboratory study using cell cultures and in vitro models. While it demonstrates proof of concept with multiple complementary experiments, it has not yet been tested in animals or humans, placing it at an early stage of the evidence hierarchy.
When this study was published
Published in 2025, this is a very recent study representing the current frontier of peptide-based drug delivery research for brain tumors.
The bigger picture
This research fits into a growing effort to use peptide-based nanotechnology for precision cancer treatment. Multifunctional delivery platforms that can cross biological barriers, target specific tumor markers, and release multiple drugs on demand represent a next-generation approach to treating cancers that resist conventional therapies. The combination of metabolic disruption and chemotherapy is also part of a broader trend toward attacking cancer through multiple mechanisms simultaneously.
Questions still open
- How will this nanofiber system perform in animal models of glioblastoma, and can it extend survival?
- What is the safety profile of the dual-drug nanofiber in healthy brain tissue?
- Could this platform be adapted to deliver other drug combinations for different brain cancers?
Common questions
What makes this nanofiber different from other drug delivery systems?
How far is this technology from being used in patients?
Read the original research
Synergistic Cancer Metabolic Therapy via Co-Delivery of 3-Bromopyruvate and Temozolomide with a Supramolecular Shuttle.
ACS applied materials & interfaces, 17(44), 60342-60360
Citation
Bellavita, Rosa; Prisco, Marina; Palladino, Sara; Barra, Teresa; Donadio, Federica; Esposito, Emanuela; Esposito, Rodolfo; Panico, Giuliana; Pisano, Jessica; Venditti, Paola; Valiante, Salvatore; Falanga, Annarita; D'Errico, Gerardino; Lombardi, Assunta; Galdiero, Stefania. (2025). Synergistic Cancer Metabolic Therapy via Co-Delivery of 3-Bromopyruvate and Temozolomide with a Supramolecular Shuttle.. ACS applied materials & interfaces, 17(44), 60342-60360. https://doi.org/10.1021/acsami.5c17607