Past the barrier

Ion pump delivers chemotherapeutic drugs directly to the brain

Tatiana Matveeva, "Scientific Russia" Despite the operation and subsequent treatment with chemotherapy and radiation therapy, most patients have relapses of malignant brain tumors.

Researchers from the University of Linkoping (Sweden) and the Medical University of Graz (Austria) have shown on cancer cells in the laboratory that the ion pump can deliver drugs more accurately, which reduces the risk of serious side effects during chemotherapy, the press service of the University of Linkoping reports. The results are published in Advanced Materials Technologies (Waldherr et al., Targeted chemotherapy of glioblastoma spheroids with an iontronic pump).

The white circle is a cross-section of a glass capillary with a diameter of just over 200 nanometers. The black dot in the center is the actual channel through which the medicine is transported. Next to the glass tube is a glioblastoma sphere. Photo: Medical University of Graz – VM.

This is the first time that an ion pump has been used to treat cancer (so far only in the laboratory). The scientists used glioblastoma cells, the most common and most aggressive type of cancer that can occur in the brain. When a brain tumor is surgically removed, small parts of the tumor often remain inside brain cells. Even high-precision surgery cannot remove these cells without damaging the surrounding healthy brain tissue. This means that radiation therapy and chemotherapy are used to stop the recurrence of the tumor.

About 30 cytostatic drugs are available in Sweden for the treatment of various types of cancer. These chemotherapeutic drugs are most often administered intravenously or in tablets. But in order to reach the brain, they must first spread through the circulatory system, and then pass through the blood-brain barrier. The walls of small blood vessels in the brain are much less permeable than blood vessels in the rest of the body, and can prevent many substances from entering the brain from the blood. Thus, only some drugs that work against cancer can pass.

Scientists from the University of Linkoping and the Medical University of Graz have developed a method by which an implanted ion pump can be used to bypass the blood–brain barrier and deliver gemcitabine – an effective chemotherapeutic agent that usually cannot pass through the blood-brain barrier - directly to the brain with high accuracy. Gemcitabine is currently used to treat pancreatic, bladder and breast cancers, where it acts by disrupting the process of cell division in fast-growing tumors. This means that gemcitabine does not affect brain cells, since they usually do not undergo cell division. 

The ion pump allows you to act only on cancer cells, leaving the neurons healthy. Also, experiments with cultured glioblastoma cells show that when using an ion pump, more cancer cells die than with conventional treatment. 

When an ion pump has to transport gemcitabine from an electrolyte reservoir to cells or a tumor, a weak current is used to "pump" the positively charged drug through the ion transfer channel. The method is known as electrophoresis. The ion pump requires only a weak current to pump gemcitabine, which is an advantage because it avoids the risk of activating brain cells and transmitting unintended nerve signals. Low current and voltage also mean that ultimately the therapeutic technology will not require large power supplies or batteries to operate.

Rainer Schindl, associate professor at the Medical University of Graz, describes other benefits: "The pressure inside the brain is extremely sensitive, and using an ion pump to transport the medicine instead of a fluid-driven device means that the pressure will not be affected. In addition, the dosage is controlled by an electric charge, which ensures that the medication is delivered extremely accurately. The next step will be to use an ion pump to evaluate various chemotherapeutic agents that have previously given too serious side effects or that cannot pass through the blood-brain barrier."

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