The device is as powerful as commercially available devices made from toxic ceramics and could lead to more effective treatments for brain tumors. — Science Daily

According to the American Cancer Society, more than 24,000 people in the United States develop brain tumors each year, and more than 18,000 Americans will die from them by 2023.

Once a cancerous brain tumor is diagnosed, the tumor is usually surgically removed, followed by chemotherapy to remove any remaining cancer cells. However, brain tumors are particularly resistant to chemotherapy because the lining of blood vessels prevents the passage of large molecules that can harm the brain. They also prevent useful chemicals and other therapeutic agents from killing brain tumor cells or treating other brain diseases. As we know, one safe and effective way to cross the blood-brain barrier is to use ultrasound to agitate the cells, creating pores large enough for the drug to pass through.

However, passing ultrasound through the thick human skull is not easy. In general, multiple high-intensity ultrasound machines are strategically placed around the skull, and he must carefully focus on the site of the tumor with an MRI machine immediately after undergoing chemotherapy at the hospital. The process takes him 5-6 hours and the powerful ultrasound waves can damage tissue. Most people with high-grade brain tumors receive chemotherapy for several months, rarely more than once. It is much more effective if the patient receives ultrasound every time he receives chemotherapy. However, MRI ultrasound is so cumbersome that it is rarely performed.

“All of this can be avoided by using devices implanted in the brain itself,” says Thanh Nguyen, a biomedical engineer. “With repeated use, the chemotherapy can penetrate the brain and kill the tumor cells.” and must be surgically removed after treatment is completed.

Nguyen’s lab specializes in biodegradable piezoelectric polymers. Piezoelectric means that the material vibrates when a small electric current is passed through it. They had previously built a safe, biodegradable piezoelectric ultrasound brain implant, but it wasn’t as strong as traditional piezoceramic. So the Nguyen Lab, with graduate students Singh T. Le and Maysam Cheolsi, co-supervised Engineering Professor Horea Iris and Dean of Engineering Kazem Kazeronian, along with postdoc Feng Lin A new technique was used to generate ultrasound of biodegradable polymers. As strong as ceramic.

The research team wanted to use crystals of glycine, a common protein in the body and an amino acid recently found to have strong piezoelectric properties. Glycine is safe and biodegradable, but too safe. It dissolves in water quickly. Glycine piezoelectric crystals are also brittle and easily crumbled, making the material very difficult to handle and produce useful ultrasonic devices.

Researchers have come up with a new solution. They grew glycine crystals and deliberately shattered them into pieces just a few hundred nanometers in size. They then took polycaprolactone (PCL), a biodegradable polymer, and spun them (under high voltage in a process called electrospinning) to create a piezoelectric film composed of nanofibers of glycine and PCL. . Under a small driving voltage (approximately 0.15 Vrms), the film can generate ultrasound waves of 334 kPa, which is almost the same as a ceramic ultrasound brain implant. The research team protected the glycine-PCL film by coating it with another biodegradable polymer. Her one of the coatings, poly-L-lactide (PLLA), takes about six weeks to degrade.

The researchers tested the device on mice with brain tumors. They treated mice with PTX (paclitaxel), a potent chemotherapy drug that is effective against brain tumors but has difficulty crossing the blood-brain barrier. Glycine-PCL ultrasound allowed PTX to bypass the blood-brain barrier, shrinking tumors and doubling the lifespan of mice with brain tumors compared with untreated mice. Also, the combination treatment of glycine-PCL ultrasound + PTX was effective when treated with PTX alone, or with PTX and ultrasound with the original less intense version of Nguyen Lab’s biodegradable ultrasound device based on PLLA. It was much more effective for mice than it was for treatment.

In addition to the aforementioned therapeutic effects, the research team tested the safety of the device already implanted in the brain for six months and found no adverse effects on the health of the mice. They now plan to begin safety and efficacy trials in large animals.

This work was funded by grants R21NS116095 and RO1NS131310 to the Nguyen Laboratory at the National Institutes of Health (NIH).