Cellular time: "brain on a chip" will help treat the most aggressive form of cancer

Scientists have developed a microfluidic "brain on a chip" system to explore a new approach to the treatment of glioblastoma, one of the most aggressive forms of brain cancer. The combination of chemotherapy and wireless optostimulation made it possible to achieve almost complete destruction of tumor cells in laboratory samples. If further research is equally successful, doctors will receive a powerful tool in the future to combat this dangerous disease, experts told Izvestia. However, it is necessary to test the approach directly in clinical trials involving patients.

Why do we need a "brain on a chip"

Researchers from the Institute of Bionic Technologies and Engineering, together with the experimental Biotherapy group at the Institute of Regenerative Medicine at Sechenov University, have developed a microfluidic platform that simulates blood flow in the brain and supports the vital functions of glioblastoma cells. Scientists have shown that an organic semiconductor device under the influence of red light stimulates the activity of ion channels in cells. New experiments have shown that a similar effect is observed in glioblastoma cells, which increases the penetration of temozolomide, one of the key drugs for the treatment of this tumor.

Photo: Global Look Press/Anna Altukhova/Russian Look

— Ion channels work like pumps — they draw molecules into the cell. Temozolomide needs to enter the nucleus to destroy the cancer cell. Red light accelerates the opening and closing of channels, the concentration of the drug in the cell increases faster, and the cell dies. In experiments, we managed to destroy up to 95-98% of glioblastoma cells, which is five times more than in control samples without stimulation," Alexander Markov, head of the study and associate professor at the Institute of Bionic Technologies and Engineering, told Izvestia.

As the researchers emphasized, this is the first brain-on-a-chip system that uses wireless optoelectronic stimulation. It does not require electrodes or inductive coils, which can cause heat and cell damage, making the technology less invasive and safer.

Photo: Global Look Press/Patrick Pleul/dpa

— Our experiments have shown that the combination of therapy with wireless stimulation enhances the effect of the drug and helps it penetrate deeper into cells. Now we are moving on to work with primary cultures and organotypic tissue sections, models that are more closely related to real brain tissue. In particular, the preliminary results on the primary aggressive culture obtained from a patient with glioblastoma also demonstrated an increased therapeutic effect," said Anna Konstantinova, a student at the Institute of Pharmacy at Sechenov University.

Mild precipitation: a new chip manufacturing plant has been created in Russia

What processes for the manufacture of microelectronics will be performed on domestic equipment

Prospects of glioblastoma therapy

Further testing of the combined therapy method on glioblastoma cell models will allow evaluating the advantages of this technology in the treatment of malignant glioblastoma in conditions of increased tumor resistance to chemotherapy, added Victoria Khoruzhaya, a student at the Institute of Pharmacy.

The brain-on-a-chip platform itself is planned to be used in the future to study other types of brain tumors. However, clinical use is still far away — scientists have to solve a number of technical problems and go through a long testing path.

Photo: Global Look Press/Simon Belcher/imageBROKER.com

The development of a microfluidic brain-on-a-chip platform for studying glioblastoma therapy opens up prospects for creating new, more effective approaches to the treatment of one of the most aggressive and difficult to treat types of brain tumors, Maxim Kotov, market expert at NTI Helsnet, oncologist at the N.N. Petrov National Research Medical Center of Oncology, told Izvestia..

"Since this technology allows us to simulate the penetration of drugs and their effect on tumor cells in conditions as close as possible to real ones, the first experiments with a combination of temozolomide and wireless optostimulation have already shown a significant increase in the antitumor effect," he said.

The main feature of this brain—on-a-chip model is a realistic reproduction of the physiological microenvironment of a tumor, including imitation of blood flow and the possibility of safe cell optostimulation, said Albert Rizvanov, head of the Center for Excellence "Personalized Medicine" at Kazan (Volga Region) Federal University, corresponding member of the Academy of Sciences of the Republic of Tatarstan.

— This allows us to bring laboratory research closer to the real processes taking place in the human body, — said the expert.

Photo: IZVESTIA/Sergey Lantyukhov

The main challenge remains the problem of targeted drug delivery and selective effects on tumor cells in the conditions of the whole organism, he said.

"To conclude that the technology can be applied in clinical practice, research will be required both on biological models of diseases and directly in clinical trials involving patients," said Alexander Zakharov, director of the Research Institute of Neuroscience at SamSMU, an expert at the NTI Center based on the university and the NTI Helsnet market.

The work is supported by a grant from the Russian Science Foundation.