ELPHI: A Next Generation Device for Brain Cancer Treatment

The diagnosis of brain cancer, also known as glioblastoma (GBM), is devastating. Due to the aggressive and strongly infiltrating growth of these tumors, conventional therapeutic measures reach their limits. Despite the combination of surgical tumor removal with chemotherapy and radiation therapy, most patients have a life expectancy of around 15 months. The team around Rainer Schindl, Linda Waldherr (both Gottfried Schatz Research Center) and Silke Patz (Neurosurgery) from the Medical University of Graz tackle this problem. Their goal is to develop a brain implant for the targeted and time-controlled delivery of new chemotherapy drugs. The idea came from Linda Waldherr when she started her PhD two years ago. "I knew about this technology and that our cooperation partners were looking for physiologically relevant application for it. I actually only mentioned the idea of using it for brain tumours, but Rainer found it exciting and asked me to investigate. We have been doing research in the area for over two years now. We had to improvise a lot with some devices and test setups. Because for our experiments there are either only very expensive products or equipment, or there are no offers at all. Sometimes I had to smile myself how much I misused typical laboratory objects for our research. But the creativity and the effort were worth it and we will publish the first results soon, says the young researcher. For their project, the Graz researchers have now set up a multidisciplinary team consisting of Swedish materials scientists from Linköping University and experts from the Medical University in the fields of neurotraumatology, neurosurgery, neuropathology and the Otto Loewi research center (see photo). Together they have the goal of developing the implant from the current initial stage in the cell culture laboratory to patient application. This innovation has two major advantages. Firstly, with this technology we can administer the chemotherapeutic agents with extreme precision - and directly and exclusively at their desired site of action. Secondly, this implant enables the use of chemotherapy drugs that cannot be used in classic intravenous therapy because they cannot cross the blood-brain barrier, explains Schindl. With this innovation in glioblastoma therapy, the researchers hope for better treatability, life-prolonging effects, and a reduction in side effects because, on the one hand, less toxic chemotherapy is used and the effectiveness of radiation therapy is to be increased. The research team was recently recognized for their revolutionary idea. The FWF`s new 1000 Ideas program aims to provide financial support and drive forward innovative and innovative high-risk projects. "This support program is tailor-made for our idea. However, if we had known that the chances of getting this application through are around 8%, we would probably not have taken part, says Silke Patz. With the help of this funding, the international research team now wants to advance prototype research and treat complex brain tumor models with the implant prototypes.

We have already done extensive outreach to the public as summarized for the first paper "Targeted Chemotherapy of Glioblastoma Spheroids with an Iontronic Pump" (for details please see: https://wiley.altmetric.com/details/103920619/news). We are currently working on a second media release for our new paper accepted in Journal of Controlled Release, and we like to share these new articles with the FWF once we have it fully written. Here we'd like to summarize the two major publications: Glioblastoma multiforme (GBM), the deadliest brain tumor, presents formidable challenges due to limited surgical options and the blood-brain barrier's (BBB) protective shield. In this project we have established a fundamental new technology to control electronically local and spatial GBM tumor treatment by highly efficient chemotherapeutic Gemcitabine (Gem) to combat proliferation of this brain tumor. In two publications in Journal of Controlled Release and Advanced Materials Technologies, our research confirms Gem's superior potency in killing GBM cells compared to the gold standard temozolomide, compared to neuronal cells exhibiting much lower sensitivity towards Gem. Leveraging the power of electronically-driven organic ion pumps ("GemIPs"), we achieved precise and targeted Gem delivery to GBM cells, demonstrating unprecedented control and efficacy. In a pivotal experiment using an avian embryonic GBM in vivo tumor system, we compared GemIP treatment with conventional metronomic administration. The results were astonishing: only GemIPs achieved significant tumor growth inhibition, while daily topical dosing did not result in any suppression of tumor growth. Both methods induced cell cycle arrest and apoptosis in GBM tumors. The main advantage is that GemIPs maintained a prolonged, high local Gem concentration near the tumor site, surpassing the transient effects of daily topical treatment. This groundbreaking approach not only overcomes the BBB but also offers long-lasting, highly localized dosing of potent chemotherapeutics, promising to revolutionize GBM adjuvant chemotherapy. Electrically-driven chemotherapy, exemplified by GemIPs, opens new frontiers in cancer treatment in general, to have a minimal surgery with only a small capillary outlet to target the tumors efficiently.