Scientists in Britain and Spain have discovered critical windows after glioblastoma surgery when the brain's defences falter, creating a rare chance to deliver powerful treatments exactly where needed. If doctors time treatment within two narrow postoperative windows identified by the researchers, existing lipid nanoparticle medicines - already approved and routinely used in oncology hospitals today - could be redeployed to deliver early, precision‑targeted therapy to the brain.
The studies, published in Science Translational Medicine on 29 July, were performed using mouse models of this largely incurable disease by a team from the Centre for Nanotechnology in Medicine and the Geoffrey Jefferson Brain Research Centre at The University of Manchester.
Glioblastoma is the most common and most aggressive brain cancer in adults and currently has no cure. Neurosurgeons will typically first remove the tumour, before treating the patient with chemoradiotherapy 4 to 6 weeks later. Because glioblastoma cells infiltrate deep into healthy brain tissue, some will always remain after surgery, fuelling the near‑inevitable return of disease, most times regrowing at the rim of the surgical resection.
The research, spearheaded by postdoctoral associate at The University of Manchester Dr Lorena Fernandes, showed experimentally that the blood‑brain barrier is disrupted after surgery, opening two short‑lived therapeutic windows at the resection margin - immediately after the operation and again 48-72 hours later. Using different mouse models and performing precise neurosurgery to remove the growing glioblastoma tumours from their brains, the team tracked fluorescently labelled, liposomal nanoparticles injected into the blood stream during the time-windows identified. The particles homed in on the resection margin with remarkable precision while other brain regions with an intact barrier showed almost no uptake.
Lipid nanoparticle medicines are based on tiny lipid-based nanoscale carriers that can ferry different cancer drugs (such as chemotherapies, radiotherapies, mRNA therapies) directly to tumours so the medicine targets the cancer cells alone. They are used to treat different types of cancer, but until now they have not been shown to be effective against this difficult to treat disease.
Chemotherapies have also largely failed in this disease due to poor crossing of the blood-brain barrier, and minimal amounts can reach the few cancer cells left over from surgery. By loading these liposome nanoparticles with the chemotherapy drug doxorubicin, the team was able to exploit these newly identified post-operative windows to achieve precise delivery in the brain, exactly where needed. Across different mouse models, a single injection of this liposomal drug was able to suppress recurrence and control the disease with little toxicity.the first half of your story here.
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 of the studies, 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 tumour 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."
- The study was funded by the Engineering and Physical Sciences Research Council and the Rosetrees Trust both in the UK, and the Severo Ochoa Centres of Excellence programme in Spain.
- The paper Targeting therapeutic nanoparticles to the glioblastoma resection margin by 6 harnessing post-operative blood-brain barrier disruption is published on Science Translational Medicine on 29 July. DOI
