Mollusk-inspired bioadhesive patch flexes its mussels against aggressive brain tumor
A bio-inspired adhesive patch puts some mussel into treating glioblastoma – the most aggressive brain tumor.
Inspired by the impressive adhesive abilities of mussels, researchers from the Institut de Neurociències of the Universitat Autònoma de Barcelona and the Institut Català de Nanociència i Nanotecnologia (both Barcelona, Spain) have designed a bioadhesive patch that selectively kills glioblastoma cells, representing a novel strategy to address recurrence of the aggressive brain cancer post-surgery.
Glioblastoma is the most common and aggressive malignant brain tumor, characterized by its rapid growth, invasion of surrounding brain tissue and resistance to conventional therapies. Current treatment options involve a combination of surgery, radiation and chemotherapy, but these frequently result in recurrence, hence the urgent need for alternative approaches.
One method could be to develop scaffolds, such as membranes or adhesive patches, designed for application immediately following tumor resection. By placing these scaffolds in the surgical bed before the wound is closed, surgeons can target any remaining cancer cells and prevent recurrence.
Glioblastoma cells often exhibit elevated reactive oxygen species (ROS), which are involved in signaling pathways that promote tumor growth, survival and resistance. As a result, modulating ROS levels could offer a promising approach for developing more effective treatments for glioblastoma. Catechol and polyphenolic-based compounds are well-known ROS modulators and also key players in natural-based adhesive structures – such as those used by mussels – and so make excellent candidates for use in advanced scaffolds.
To that end, the researchers developed a simple process to produce bioinspired adhesive membranes that could be used as a patch to address glioblastoma recurrence after surgery.
They combined different catechol and phenolic-based molecules with hexamethylenediamine to create six membranes. After a 48-hour incubation period, floating membranes formed at the air–water interface and were investigated in a series of tests.
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In an in vitro cytotoxicity assay using the human glioblastoma cell line LN229, one membrane, containing catechin, demonstrated a remarkable anti-tumor effect, inducing cell death in approximately 90% of the cancer cells. The remaining membranes failed to induce substantial cell death, with cytotoxicity rates remaining below 5%.
X-ray photoelectron spectroscopy and scanning electron microscopy revealed the cathechin membrane’s robust chemical and morphological stability, as well as its eventual biodegradability, which would make it ideal for application in the human body.
Moreover, when the membrane was suspended with Methicillin-Resistant Staphylococcus aureus and Escherichia coli, it demonstrated exceptional antibacterial activity, reducing colony-forming units by over 99.999% and 99.99%, respectively.
The membrane was then placed as patches on an ex vivo pig brain, adhering under high humidity conditions akin to the environment of a surgical site.
When the cathechin membrane was tested in LN229 spheroids that mimic a tumor-like environment, it was found to significantly reduce the invasiveness of the spheroids by inhibiting migration and inducing cell damage.
Additionally, proteomic studies shed some light on the mechanisms underlying the membrane’s performance, suggesting that it induces changes in cellular shape, responses to ROS and disruptions in mitochondrial function and energy production.
“These materials show high antimicrobial activity and excellent biocompatibility, which would help prevent infections and promote proper wound healing. Combined with their extremely low production cost and the simplicity of their fabrication, they represent a viable option in terms of future development, scalability, and potential investor interest,” first author Jose Bolaños-Cardet concluded.