Researchers from the BIST Community centre ICN2 and the University of Manchester have identified specific time windows after glioblastoma surgery during which the blood–brain barrier becomes more permeable. This creates an opportunity to deliver nanoparticle-based therapeutics more effectively. The work is published in Science Translational Medicine.
Glioblastoma is a particularly aggressive type of malignant brain tumour and the most common primary brain cancer in adults. Surgery, known as tumour resection, is the standard-of-care frontline treatment in many cases, but it is not curative. Cancer cells often remain embedded in the surrounding tissue after surgery and can rapidly regrow, causing the disease to return close to the periphery of the surgical margin. Although drug treatments are also available, many have limited effectiveness because they cannot reach the tumour site in sufficient quantities. This is largely due to the blood–brain barrier, a selective protective layer that prevents many substances from entering the brain.
A study published in the journal Science Translational Medicine this week has shown that surgery itself creates a therapeutic opportunity that has so far remained unexplored. The research, conducted by scientists at the Centre for Nanotechnology in Medicine of the University of Manchester, led by Dr Lorena Fernandes and Dr Thomas Kisby, in collaboration with the Nanomedicine Lab at ICN2, identified two specific periods during which the blood–brain barrier remains disrupted, allowing treatments to penetrate the brain more effectively.
These two periods occur immediately after surgery and again between 48 and 72 hours later. During these two temporal windows, the barrier becomes more permeable to nanotherapies.
The key: making use of precise therapeutic windows
The researchers’ strategy involved using these ‘time windows’ to administer lipid nanoparticle encapsulated doxorubicin, a chemotherapy drug, and evaluate its therapeutic effectiveness. More specifically, small lipid-based vesicles, called liposomes, loaded with doxorubicin were administered intravenously at the precise times when the blood–brain barrier was disrupted.
Results obtained using different mouse models of glioblastoma, in which tumours had been surgically removed, showed that the treatment could cross the blood–brain barrier more easily. Significantly larger amounts of the drug accumulated around the surgical resection margin, where a few remaining cancer cells may pose a major risk of recurrence following surgery. In these preclinical models, the treatment reduced tumour growth and clearly delayed or entirely prevented recurrence of the disease. In some animals, a single dose was enough to produce significant results.
According to ICREA Prof. Kostas Kostarelos, leader of the ICN2 Nanomedicine Lab and one of the study’s senior authors: “These results open the door to a new way of approaching post-operative treatment for glioblastoma using already clinically approved nanotherapies. This could include nanoparticle-based therapeutics, including gene therapies or immunotherapies, with the aim of targeting them precisely at the surgical marginal zone to achieve better treatment outcomes.”
The study also showed that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), a technique already used in clinical practice, could help to identify and confirm precisely when the blood–brain barrier becomes permeable. This could be highly valuable for optimising and personalising treatment for individual patients.
In short, these findings propose a new approach to the early treatment of glioblastoma. Rather than developing new drugs or nanotherapies, the strategy involves administering existing treatments at the most opportune biological moment.
While clinical trials are still required to confirm these preclinical findings in human patients, this study represents an important step forward in a disease that suffers from failure in extending survival and has not allowed adoption of new therapeutics over the last 20 years. In the future, this strategy could potentially be extended to the treatment of other types of brain tumours that involve surgical treatment.
Reference article:
Fernandes, L. F.; Peeyatu, C.; Thompson, L. A.; Dickie, B. R.; Ho, Y. S.; Hernandez, N.; Lozano, N.; Kostarelos, K; and Kisby, T. Targeting therapeutic nanoparticles to the glioblastoma resection margin by harnessing postoperative blood-brain barrier disruption. Science Translational Medicine. (2026). DOI: 10.1126/scitranslmed.adv87
