New Technique Shows Promise in Fighting Brain Cancer

Summary: Researchers developed a new method, burst sine wave electroporation (B-SWE), to treat glioblastoma, a fast-growing brain tumor. B-SWE disrupts the blood-brain barrier more effectively than traditional methods, allowing cancer drugs better access to the brain.

This technique could enhance treatment by minimizing damage to healthy brain tissue while targeting cancer cells. The study highlights a promising advance in brain cancer therapy.

Key Facts:

  1. B-SWE disrupts the blood-brain barrier more effectively than conventional methods.
  2. The technique may allow more cancer-fighting drugs to enter the brain.
  3. B-SWE minimizes damage to healthy brain tissue while targeting cancer cells.

Source: Virginia Tech

Tackling brain cancer is complicated, but groundbreaking new research could help add another tool to the cancer-fighting arsenal.

A team from Georgia Tech and Virginia Tech published a paper in APL Bioengineering in May that explores a new option that could one day be used to target glioblastoma, a deadly and fast-growing brain tumor.  

Supported by National Institutes of Health grants, this work stems from past research on high frequency irreversible electroporation, better known as H-FIRE. H-FIRE is a minimally invasive process that uses non-thermal electrical pulses to break down cancer cells.

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. Credit: Neuroscience News

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,” 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 wave typically used with H-FIRE performs double dut: It disrupts the blood-brain barrier around the tumor site while destroying cancer cells. However, this was the first study to use a sinusoidal wave to disrupt the barrier. This new modality is called burst sine wave electroporation (B-SWE).

The researchers used a rodent model to study the effects of the sinusoidal wave versus the more conventional, square-shaped wave. They found that B-SWE resulted in less damage to cells and tissue but more 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 study, the researchers hit a snag: In addition to more blood-brain barrier disruption, they found that the sinusoidal wave also caused more neuromuscular contractions.

These muscle contractions run the risk of damaging the organ. However, by tweaking the dose of B-SWE, they were able to reduce the contractions while providing a level of blood-brain barrier disruption similar to that of a higher dose.

The next step in this research is to study the effects of B-SWE using an animal model of brain cancer to see how the sinusoidal waveform stands up against the conventional H-FIRE technique.

The project was spearheaded by first author Sabrina Campelo while she completed her Ph.D. at the Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences. Campelo is now a postdoctoral fellow at the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.

About this brain cancer research news

Author: Andrew Mann
Source: Virginia Tech
Contact: Andrew Mann – Virginia Tech
Image: The image is credited to Neuroscience News

Original Research: Open access.
Burst sine wave electroporation (B-SWE) for expansive blood–brain barrier disruption and controlled non-thermal tissue ablation for neurological disease” by John Rossmeisl et al. ALP Bioengineering


Abstract

Burst sine wave electroporation (B-SWE) for expansive blood–brain barrier disruption and controlled non-thermal tissue ablation for neurological disease

The blood–brain barrier (BBB) limits the efficacy of treatments for malignant brain tumors, necessitating innovative approaches to breach the barrier.

This study introduces burst sine wave electroporation (B-SWE) as a strategic modality for controlled BBB disruption without extensive tissue ablation and compares it against conventional pulsed square wave electroporation-based technologies such as high-frequency irreversible electroporation (H-FIRE).

Using an in vivo rodent model, B-SWE and H-FIRE effects on BBB disruption, tissue ablation, and neuromuscular contractions are compared.

Equivalent waveforms were designed for direct comparison between the two pulsing schemes, revealing that B-SWE induces larger BBB disruption volumes while minimizing tissue ablation.

While B-SWE exhibited heightened neuromuscular contractions when compared to equivalent H-FIRE waveforms, an additional low-dose B-SWE group demonstrated that a reduced potential can achieve similar levels of BBB disruption while minimizing neuromuscular contractions.

Repair kinetics indicated faster closure post B-SWE-induced BBB disruption when compared to equivalent H-FIRE protocols, emphasizing B-SWE’s transient and controllable nature.

Additionally, finite element modeling illustrated the potential for extensive BBB disruption while reducing ablation using B-SWE.

B-SWE presents a promising avenue for tailored BBB disruption with minimal tissue ablation, offering a nuanced approach for glioblastoma treatment and beyond.