July 10, 2023 – Scientists have developed a biodegradable implant that helps chemotherapy drugs penetrate the blood-brain barrier and deliver a direct hit on brain tumors.
It’s the latest advance in a rapidly growing field using ultrasound – high-frequency sound waves undetectable to humans – to fight cancer and other diseases.
The problem addressed by the researchers is the blood-brain barrier, a nearly impenetrable blood vessel lining that keeps harmful molecules from passing into the brain from the blood. But this lining can also block chemo drugs from reaching cancer cells.
So the scientists implanted one-centimeter-square devices into the skulls of mice, directly behind the tumor site. The implants generate ultrasound waves, loosening the barrier and allowing the drugs to reach the tumor. The sound waves leave healthy tissue undamaged.
“You inject the drug into the body and turn on the ultrasound at the same time. You're going to hit precisely at the tumor area every single time you use it," said lead study author Thanh Nguyen, PhD, an associate professor of mechanical engineering at the University of Connecticut.
The drug used in the study was paclitaxel, which normally struggles to get through the blood-brain barrier. The tumors shrank, and the mice doubled their lifetime, compared to untreated mice. The mice showed no bad health effects 6 months later.
Breaking Through the Blood-Brain Barrier
The biodegradable implant is made of glycine, an amino acid that’s also strongly piezoelectric, meaning it vibrates when subjected to an electrical current. To make it, researchers cultivated glycine crystals, shattered them into pieces, and finally used a process called electrospinning, which applies a high electrical voltage to the nanocrystals.
Voltage flows to the implant via an external device. The resulting ultrasound causes the tightly adhered cells of the blood-brain barrier to vibrate, stretching them out and creating space for pores to form.
“That allows in very tiny particles, including chemo drugs,” said Nguyen.
His earlier biodegradable implant broke apart from the force, but the new glycine implant is more flexible, stable, and highly piezoelectric. It could be implanted after a patient has surgery to remove a brain tumor, to continue treating residual cancer cells. The implant dissolves harmlessly in the body over time, and doctors can control its lifespan.
A New Wave of Uses for Ultrasound
Nguyen’s study builds on similar efforts, including a recent clinical trial of a nonbiodegradable implant for treating brain tumors. Ultrasound can focus energy on precise targets in the body.
It’s like "using a magnifying glass to focus multiple beams of light on a point and burn a hole in a leaf,” said Neal Kassell, MD, founder and chairman of the Focused Ultrasound Foundation. This approach spares adjacent normal tissue, he said.
Doctors now understand more than 30 ways that ultrasound interacts with tissue – from destroying abnormal tissue to delivering drugs more effectively to stimulating an immune response. A decade ago, only five such interactions were known.
This opens the door for treating “a wide spectrum of medical disorders,” from neurodegenerative diseases like Alzheimer’s and Parkinson’s to difficult-to-treat cancers of the prostate and pancreas, and even addiction, said Kassell.
Kassell envisions using focused ultrasound to treat brain tumors as an alternative (or complement) to surgery, chemotherapy, immunotherapy, or radiation therapy. In the meantime, implants have helped show “the effectiveness of opening the blood-brain barrier,” he said.
Nguyen’s team plans on testing the safety and efficacy of their implant in pigs next. Eventually, Nguyen hopes to develop a patch with an array of implants to target different areas of the brain.