Nanoparticles to treat incurable brain tumors?

Can a nanocapsule transport a drug to the brain area damaged by a stroke? Can a molecule be modified to attack brain tumor cells? Advanced materials are key to scientific innovation that could improve the treatment of brain diseases, especially by making them more precise and with fewer side effects.

This is the case of two leading projects of theBarcelona Institute of Materials Sciences (ICMAB), a CSIC center: the first, that of the spin-off LabsinLove (LiL), with the participation of members of the Inorganic Materials and Catalysis group in collaboration with the University of Granada; and the second, the End-STROKE project (funded by La Marató de TV3), with the participation of members of the Nanoparticles and Nanocomposites group.

From nuclear power plants to hospitals

Glioblastoma is one of the most aggressive brain tumors. Currently, it is treated with surgery and subsequent radiotherapy or chemotherapy. In the LabsinLove They are investigating treatment with Boron Neutron Capture Therapy (BNCT), a therapy that consists of placing a target (boron) in the tumor tissue and irradiating it with neutrons that destroy only the cells with boron through nuclear reaction without causing damage to healthy tissue, unlike radiotherapy, which is not radiotherapy.

This therapy has not been applied more widely because until recently the necessary neutrons were only produced in reactors at nuclear power plants. This meant that "you needed to have the facilities near a nuclear power plant and take the person there to treat them," explains ICMAB researcher Rosario Núñez. Fortunately, there are now compact particle accelerators that generate these neutrons and it is "a simple installation that you can set up in a hospital."

Even so, the therapy requires further research into irradiation and neutron dose customization, as well as with regard to the boron compound itself. Currently, "compounds are used that have a single boron atom (borophenylalanine or BPA), which is not very soluble, and you need to inject a very large amount," explains the researcher, who is working to develop "boron compounds that are more selective and have a higher content of this chemical element," and that are more elemental. This would allow them to reduce the dose and minimize its side effects. Furthermore, these molecules are designed to be detectable with microscopy, making BNCT also a diagnostic tool.

"I would love to see some fruit from all this in a few years, before I retire," Núñez confesses with enthusiasm, but admits that there is still time before the therapy reaches patients, despite the fact that the University of Granada has already conducted trials with BPA conjugates with good results.

Sending nanocapsules to the brain

Stroke is the second leading cause of death worldwide and the leading cause of disability in Europe, according to the Global Burden of Disease (GBD) report by the Institute for Health Metrics and Evaluation (IHME). According to the Spanish Society of Neurology, 80% of strokes occurring in Spain are ischemic, meaning they occur when a clot blocks blood flow to the brain. While current treatments for this type of stroke focus on restoring blood flow by removing the clot that causes it rather than repairing damaged brain tissue, End-STROKE proposes the administration of nanocapsules that release bioactive molecules derived from stem cells to regenerate tissue, memory, speech, and psychomotor movements.

The intervention, which is being tested on mice, is performed with a microcatheter that travels through the arteries to the blocked area and directly reaches the affected area of the brain, as is already the case with other current treatments. However, this pioneering research now proposes combining endovascular intervention with nanomedicine and nanomaterial treatments.

"One of the problems with nanomaterials is that when administered intravenously, they travel through the circulatory system very quickly to other organs and can have side effects," explains Ana Rossell, a researcher at the Vall d'Hebron Research Institute (VHIR), whose first objective is to demonstrate that they are "more efficient and effective."

These nanocapsules, which are a quarter of a micrometer in size and are made from biodegradable and biocompatible polymers, contain secretome (the substances released by stem cells), which has several functions: "Replacing damaged endothelial cells and thus the surrounding cells." The advantage of nanocapsules is that "they allow the contents to be released in a sustained manner," which also prevents the drug from spreading beyond the area of interest. In addition, they contain a magnet that helps researchers retain them where the magnetic field is located.

This research is planned for three years, but for Rosell, that's too short. "If all goes well and the results are good, and all the preclinical studies can be completed, it has a fifteen-year runway and will require collaboration and support from the pharmaceutical and biotechnology industries," he admits.