When low doses of anticancer drugs are continuously administered near malignant brain tumors using so-called iontronic technology, the growth of cancer cells is significantly reduced. Researchers from Linköping University and the Medical University of Graz have demonstrated this in experiments on bird embryos. The results are a step closer to new types of effective treatments for severe forms of cancer.
Neurons – illustration photo. Image credit: Pixabay (Pixabay Free License)
Malignant brain tumors often recur despite surgery and post-treatment with chemotherapy and radiation. This is because cancer cells can “hide” deep in tissues and then grow back. The most effective drugs cannot cross the blood-brain barrier – a tight network surrounding the blood vessels of the brain that prevents many substances in the blood from entering. As a result, there are very few options available to treat aggressive brain tumors.
In 2021, a research group from Linköping University and the Medical University of Graz demonstrated how an ion pump could be used to locally deliver drugs and inhibit cell growth of a particularly malignant and aggressive form of brain cancer: glioblastoma. At that time, experiments were conducted on tumor cells in a petri dish.
Proven concept
Now, the same research group has taken another step toward using this technology in clinical cancer treatment. By allowing glioblastoma cells to grow from undeveloped bird embryos, new treatment methods can be tested on living tumors. The researchers showed that cancer cell growth was reduced when low doses of powerful drugs (gemcitabine) were continuously delivered using an iontronic pump directly adjacent to the brain tumor.
“We have already shown that the concept works. Now we are using a model with a living tumor and we can see that the pump delivers the drug very effectively. So even though it is a simplified human model, we can say with more certainty that it works,” says Daniel Simon, professor of organic electronics at Linköping University.
The concept behind a future treatment for glioblastoma involves surgically implanting an iontronic device directly into the brain, near the tumor. This approach allows for the use of low doses of powerful drugs while bypassing the blood-brain barrier. Precise dosing, both in terms of location and timing, is crucial for effective treatment. Additionally, this method can minimize side effects since the chemotherapy does not need to circulate throughout the body.
Treatment of various forms of cancer
Beyond brain tumors, researchers hope iontronics can be applied to many types of hard-to-treat cancers.
“This becomes a very persistent treatment from which the tumor cannot hide. Even if the tumor and surrounding tissues try to eliminate the drug, the materials and control systems we use in iontronics can continuously deliver a locally high concentration of drug to tissues adjacent to the tumor,” says Theresia Arbring Sjöström, a researcher at the Research Laboratory for Organic Electronics at Linköping University.
The researchers compared continuous drug delivery through the pump to once-daily dosing, which more closely resembles how chemotherapy is given to patients today. They found that tumor growth decreased with the ionic treatment but not with the daily dose approach, even though the daily dose was twice as strong.
More research needed
These experiments were conducted on bird embryos at an early stage of development. According to Linda Waldherr, a researcher at the Medical University of Graz and a visiting researcher at LiU, this model is a good bridge to larger animal experiments:
“In bird embryos, some biological systems work in a similar way to those in living animals, such as the formation of blood vessels. However, we do not yet need to surgically implant devices into them. This demonstrates that the concept works, although there are still many challenges to overcome,” she says.
The researchers estimate that human trials could be feasible within five to ten years. The next steps are to develop more materials that will allow surgical implantation of iontronic pumps. Further experiments will also be conducted on rats and larger animals to further evaluate this treatment method.
The study was mainly funded by the Austrian Science Fund, the European Union’s Horizon Europe programme, the Swedish Foundation for Strategic Research, the Knut and Alice Wallenberg Foundation and the European Research Council. Theresia Arbring Sjöström, Tobias Abrahamsson, Magnus Berggren and Daniel Simon are shareholders of the company OBOE IPR AB which holds the patents related to iontronic technology.
Article: Continuous Iontronic Chemotherapy Reduces Brain Tumor Growth in Avian Embryonic Models in VivoVerena Handl, Linda Waldherr, Theresia Arbring Sjöström, Tobias Abrahamsson, Maria Seitanidou, Sabine Erschen, Astrid Gorischek, Helena Worcester , Tamara Tomin, Sophie Elisabeth Honeder, Joachim Distl, Waltraud Huber, Martin Asslaber, Ruth Birner-Grünberger , Ute Schäfer, Magnus Berggren, Rainer Schindl, Silke Patz, Daniel T. Simon, Nassim Ghaffari-Tabrizi-Wizsy ; Controlled release diary; published online April 11, 2024. DOI: 10.1016/j.jconrel.2024.03.044
Written by Anders Törneholm
Source: Linköping University
Originally published in The European Times.
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