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IMAGE: An ion pump can deliver cytostatics extra precisely in the brain, which provides much less extreme antagonistic results in chemotherapy.
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Credit: Thor Balkhed

Despite surgical procedure and subsequent remedy with chemotherapy and radiation, the majority of sufferers expertise recurrence of malignant brain tumours. Researchers at Linköping University, Sweden, and the Medical University of Graz, Austria, have proven in cells in tradition that an ion pump can deliver medication extra precisely, which provides much less extreme antagonistic results in chemotherapy. The outcomes have been revealed in Advanced Materials Technologies.

“This is the first time an ion pump has been tested as a possible method to treat malignant brain tumours. We used cancer cells in the lab, and the results are extremely promising. However, it will probably take five to ten years before we see this new technology used in treatments for brain tumours”, says Daniel Simon, affiliate professor at the Laboratory of Organic Electronics at the Department of Science and Technology at Linköping University .

The scientists have used cells from glioblastoma, which is the commonest and most aggressive sort of most cancers that may come up in the brain. When a brain tumour is surgically eliminated, small components of the tumour are sometimes left behind, embedded between the brain cells. Even high-precision surgical procedure can’t take away these cells with out damaging the surrounding wholesome brain tissue. This implies that radiation remedy and chemotherapy are used to cease the recurrence of the tumour.

In Sweden, round 30 cytostatics can be found to deal with several types of most cancers. These chemotherapy agents are most frequently given both intravenously or as a pill. But so as to attain the brain, they need to first unfold by way of the circulatory system after which cross by way of the blood-brain barrier. The partitions of the small blood vessels in the brain are a lot much less permeable than blood vessels in the remainder of the physique, and may forestall many substances in the blood getting into the brain. Thus, only some medication that work in opposition to most cancers can cross by way of.

Scientists at Linköping University and at the Medical University of Graz have now developed a technique wherein an implanted ion pump can be utilized to get round the blood-brain barrier and provide gemcitabine – a particularly efficient chemotherapy agent that can’t usually cross the blood-brain barrier – instantly into the brain with excessive precision. Gemcitabine is at present used to deal with cancers in the pancreas, bladder and breast, the place it acts by disrupting the cell division course of in quickly rising tumours. This implies that gemcitabine doesn’t have an effect on brain cells, since these don’t, typically, endure cell division.

“The traditional glioblastoma treatment currently used in the clinics harms both cancer and neuronal cells to the same extent. However, with the gemcitabine ion pump, we tackle only the cancerous cells, while neurons stay healthy. In addition, our experiments on cultured glioblastoma cells show that more cancer cells are killed when we use the ion pump than when we use manual treatment”, says Linda Waldherr, postdoctoral fellow at the Medical University of Graz. She has carried out the research along with researchers at Linköping University.

When the ion pump is to transport gemcitabine from an electrolyte reservoir into cells or a tumour, a low present is used to “pump” the positively charged drug by way of an ion transport channel. The methodology is named electrophoresis. The ion pump wants solely a low present to pump the gemcitabine, which is a bonus because it avoids the threat that brain cells are activated and transmit unintended nerve alerts. The low present and voltage additionally imply that eventual therapeutic know-how is not going to require giant energy provides or batteries to function.

Rainer Schindl, affiliate professor at the Medical University of Graz, describes different benefits.

“The pressure inside the brain is extremely sensitive, and using an ion pump to transport the drug instead of a fluid-driven device means that the pressure is not affected. Also, the dosage is controlled by electrical charging, which makes the supply of the chemotherapy agent extremely precise. The next step will be to use the ion pump to evaluate different chemotherapy agents that have previously given adverse effects that are too serious or that are unable to pass the blood-brain barrier”, he says.

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Principal funding our bodies for the analysis have been The Austrian Science Fund, the Knut and Alice Wallenberg Foundation, and the Swedish Foundation for Strategic Research.

The article: Targeted chemotherapy of glioblastoma spheroids with an iontronic pump Linda Waldherr, Maria Seitanidou, Marie Jakešová, Verena Handl, Sophie Honeder, Marta Nowakowska, Tamara Tomin, Meysam Karami Rad, Tony Schmidt, Joachim Distl, Ruth Birner-Gruenberger, Gord von Campe, Ute Schäfer, Magnus Berggren, Beate Rinner, Martin Asslaber, Nassim Ghaffari-Tabrizi-Wizsy, Silke Patz, Daniel T. Simon, Rainer Schindl Advanced Materials Technologies 2021 doi: 10.1002/admt.202001302

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