New nano-based treatment for brain cancer shows promise
Patients with incurable glioblastoma multiforme (GBM) die from recurrent tumours which grow from cells which have survived the first round of treatment. The current treatment is neurosurgery followed by radiation and the administration of the drug temozolomide. However, as the cancer penetrates deeply into healthy brain tissue, surgery cannot remove it all. Additionally, the blood-brain barrier stops chemotherapy reaching the remaining cells, from which new tumours develop. The EU-funded TargetGBM project has developed nanoparticles covered with a special coating to prevent them from entering other cells and with molecules that selectively target tumour cells. Crucially, these nanoparticles can enter cells in the blood-brain barrier and so could potentially also cross it. “If we validate our results in mice, this treatment could offer an important step towards providing an efficient cure for brain diseases, including tumours,” says Salvador Borrós, project coordinator from IQS, the project host.
Targeted nanotherapy
When it comes to treating residual cancer cells left after neurosurgery, chemotherapy does not reach all of the diseased cells and is often beset by complications. By contrast, intravenous treatment could reach residual tumour cells if able to cross the blood-brain barrier. Targeted non-viral delivery systems have shown promise to transport therapies across biological barriers, with reduced side effects as they only target diseased cells. The TargetGBM team developed a nanosystem capable of selectively introducing a treatment, in the form of genetic material, into target cells. But the property that enables the nanoparticles to package the genetic material – the positive charge of the polymer – also enables them to enter any cell. So, the team had to develop a coating that prevents this. Once achieved, the next step was to create new molecules capable of directing the nanoparticle to target tumour cells only. These molecules, made of peptides and antibodies, were then fixed to the nanoparticle surface. The results from testing have proven promising. “We have observed reduced non-target cell penetration by the coated nanoparticles and highly efficient selective entry of target cells, thanks to the targeting molecules. The nanoparticles can also enter cells in the blood-brain barrier, the first step towards being able to cross it,” adds Benjamí Oller-Salvia, former fellow and principal investigator of the project.
An adaptable modular methodology
The results of TargetGBM align well with priorities of the European Commission which has identified health, including the treatment of cancer, as a key societal challenge, along with biotechnology – including gene therapy and nanotechnology – as a key enabling technology. “While the results are promising, we are far from a final application. We are currently optimising the nanoformulations to target cancer stem cells – the cells most resistant to current treatments and responsible for tumour relapses. If we get encouraging results in mice, we will seek investment for preclinical trials,” explains Oller-Salvia. The team aims to commercially protect and potentially market several of their engineered components, including the coating, the targeting molecules and the method for anchoring molecules to the nanoparticle. As well as improving the treatment of GBM, the project’s modular nanobiotechnological system, or elements of it, could be used to treat other types of cancers, or even other diseases. The work undertaken during TargetGBM, supported by the Marie Skłodowska-Curie Actions programme, has already helped secure funding for a new research programme on Protein Targeted Nano- and Biotherapeutics at IQS led by Oller-Salvia.
Keywords
TargetGBM, glioblastoma multiforme, brain, cancer, nano, chemotherapy, blood-brain barrier, tumour, genetic, cells