Brain cancer ‘Achilles heel’ uncovered after glioblastoma surgery

Scientists in the UK and Spain have identified two brief time windows after glioblastoma surgery when the blood-brain barrier becomes temporarily disrupted, revealing a critical vulnerability that could allow precise delivery of existing lipid nanoparticle cancer medicines directly to the brain.

The peer-reviewed, experimental mouse study¹ led by researchers at the Centre for Nanotechnology in Medicine and the Geoffrey Jefferson Brain Research Centre at The University of Manchester, working with colleagues at the Catalan Institute of Nanoscience and Nanotechnology in Barcelona, suggests that carefully timed, postoperative nanoparticle-based therapies could help prevent glioblastoma recurrence at the surgical margin.

An urgent need for better glioblastoma treatment

Glioblastoma is the most common and most aggressive adult brain cancer and currently has no cure. Standard treatment involves neurosurgeons first removing as much of the tumor as possible, followed by chemoradiotherapy 4 to 6 weeks later.

However, glioblastoma cells infiltrate deep into healthy brain tissue, meaning some cancer cells always remain after surgery. These residual cells typically drive tumor regrowth at the rim of the surgical resection, leading to almost inevitable disease recurrence.

Mapping postoperative blood-brain barrier disruption

The new research, conducted in mouse models of glioblastoma, was spearheaded by Dr. Lorena Fernandes, a postdoctoral associate at The University of Manchester. The team performed precise neurosurgery to remove growing glioblastoma tumors from the brains of mice. They then tracked fluorescently labelled liposomal nanoparticles injected into the bloodstream at different time points after surgery.

The experiments showed that the blood-brain barrier at the resection margin is disrupted in two short-lived therapeutic windows: immediately after surgery and again 48–72 hours later. During these windows, the liposomal nanoparticles homed in on the resection margin with remarkable precision, while other brain regions with an intact blood-brain barrier showed almost no uptake.

Lipid nanoparticle medicines: Repurposing existing oncology drugs

Lipid nanoparticle medicines use tiny lipid-based nanoscale carriers to transport cancer drugs, such as chemotherapies, radiotherapies or mRNA therapies, directly to tumors. These formulations are already approved and routinely used in oncology hospitals to treat several types of cancer.

Until now, however, lipid nanoparticle therapies have not been shown to be effective against glioblastoma, largely because most medicines struggle to cross the intact blood-brain barrier and reach residual cancer cells after surgery.

Targeted chemotherapy delivery during postoperative windows

To test whether the newly identified postoperative windows could be exploited therapeutically, the researchers loaded liposomal nanoparticles with the chemotherapy drug doxorubicin. By administering a single injection of this liposomal drug during the disrupted blood-brain barrier windows, they achieved precise delivery of chemotherapy to the resection margin in the brain.

Across different mouse models, this approach suppressed tumor recurrence and controlled disease progression with little toxicity, suggesting that timing is critical for effective, localized treatment of glioblastoma following surgery.

Principal Investigator Dr. Thomas Kisby, CRUK Career Development Fellow at The University of Manchester, said, “For the first time, we’ve shown that glioblastoma surgery briefly exposes a vulnerability we can exploit. If treatment is timed during specific windows we identified, it is able to halt the disease significantly before it regrows.

“We suggest that the hours and days immediately after surgery may hold the key to stopping glioblastoma from returning. It also raises the possibility that other established medicines could be redeployed in smarter, more strategic ways.”

Co-Principal Investigator Professor Kostas Kostarelos, from The University of Manchester and the Catalan Institute of Nanoscience and Nanotechnology in Barcelona, said, “The study has the potential to open a new frontier in postoperative cancer care. We propose the re-framing of post-operative treatment that uses the latest nanoparticle-based medicines, including lipid nanoparticle drugs, immunotherapies, or genetic therapies, to target the rim of the surgical resection, which is the area of the brain where the tumor generally recurs, compromising survival.”

“We hope and actively fund-raise for the next stage in the development of this technology to move on from preclinical mouse models and trial this potentially redefining therapeutic approach in patients.”

References

1. Fernandes LF, Peeyatu C, Thompson LA, Dickie BR, et al. Targeting therapeutic nanoparticles to the glioblastoma resection margin by harnessing postoperative blood-brain barrier disruption. Science Translational Medicine, 29 Jul 2026, Vol 18, Issue 860.

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