Burst sine wave electroporation was discovered to produce less damage to cells and tissue but more disruption of the blood-brain barrier. Tackling brain cancer is difficult, but innovative new study may help add another tool to the cancer-fighting arsenal.
In May, a team from Georgia Tech and Virginia Tech published an article in APL Bioengineering that investigated a novel possibility for treating glioblastoma, a dangerous and rapidly growing brain tumor.
This breakthrough, which is supported by National Institutes of Health funds, is the result of previous research on high frequency irreversible electroporation, or H-FIRE. H-FIRE is a minimally invasive procedure that uses non-thermal electrical pulses to demolish cancer cells.
Treating any type of cancer isn’t easy, but when it comes to brain cancers, the blood-brain barrier adds an extra challenge. The barrier defends the brain against toxic material – but that’s not always a positive thing.
Mother Nature designed it to prevent us from poisoning ourselves, but unfortunately, the way that works, it also excludes about 99 percent of all small-molecule drugs from entering the brain and achieving adequate concentrations to elucidate their therapeutic effect. That’s particularly true for chemotherapeutics, biologics, or immunotherapies.
John Rossmeisl
“Mother Nature designed it to prevent us from poisoning ourselves, but unfortunately, the way that works, it also excludes about 99 percent of all small-molecule drugs from entering the brain and achieving adequate concentrations to elucidate their therapeutic effect. That’s particularly true for chemotherapeutics, biologics, or immunotherapies,” said John Rossmeisl, the Dr. and Mrs. Dorsey Taylor Mahin Professor of Neurology and Neurosurgery at the Virginia-Maryland College of Veterinary Medicine. Rossmeisl is one of the paper’s coauthors.
The square-shaped pulse commonly utilized with H-FIRE has a dual purpose: it breaches the blood-brain barrier around the tumor site while eliminating cancer cells. However, this was the first study to use a sinusoidal pulse to break down the barriers. This new technique is known as burst sine wave electroporation (B-SWE).
The researchers utilized a rodent model to compare the effects of the sinusoidal wave to the more common square-shaped wave. They discovered that B-SWE caused less harm to cells and tissue but increased disruption of the blood-brain barrier.
In some clinical cases, both ablation and blood-brain barrier disruption would be ideal, but in others, blood-brain barrier disruption may be more important than destroying cells. For example, if a neurosurgeon removed the visible tumor mass, the sinusoidal waveform could potentially be used to disrupt the blood-brain barrier around the site, allowing drugs to enter the brain and eliminate the last of the cancer cells. B-SWE could result in minimal damage to the healthy brain tissue.
Research indicates that the conventional square waveforms show good blood-brain barrier disruption, but this study finds even better blood-brain barrier disruption with B-SWE. This could allow more cancer-fighting drugs to access the brain.
“We thought we had that problem solved, but this shows you that with some forward thinking, there’s always potentially better solutions,” said Rossmeisl, who also serves as associate head of the Department of Small Animal Clinical Sciences.
During the investigation, the researchers encountered a problem: in addition to higher blood-brain barrier rupture, the sinusoidal wave induced more neuromuscular contractions. These muscle contractions pose a danger of harming the organ. However, by adjusting the dose of B-SWE, scientists were able to minimize contractions while achieving a level of blood-brain barrier disruption comparable to a greater dose.
The next stage in this research is to investigate the effects of B-SWE on an animal model of brain cancer to evaluate how the sinusoidal waveform compares to the usual H-FIRE approach.
