summary: Researchers have developed a new method, called burst sine wave electroporation (B-SWE), to treat glioblastoma, a fast-growing type of brain cancer, that disrupts the blood-brain barrier more effectively than conventional methods, allowing anti-cancer drugs to better reach the brain.
“This technique has the potential to enhance treatment by targeting cancer cells while minimizing damage to healthy brain tissue. The study highlights a promising advance in brain cancer treatment.”
Key Facts:
- B-SWE disrupts the blood-brain barrier more effectively than conventional methods.
- This technique may enable more anti-cancer drugs to enter the brain.
- B-SWE targets cancer cells while minimizing damage to healthy brain tissue.
sauce: Virginia Tech
Tackling brain tumors is complex, but groundbreaking new research could add another tool to the cancer-fighting arsenal.
A team from Georgia Tech and Virginia Tech APL Bioengineering The paper, published in May, explores new options for potentially targeting glioblastoma, a type of brain cancer that is deadly and rapidly progressing.
The research, supported by a grant from the National Institutes of Health, grew out of previous work on radiofrequency irreversible electroporation, better known as H-FIRE, a minimally invasive process that uses non-thermal electrical pulses to destroy cancer cells.
Treating any type of cancer is not easy, but brain tumors present an added challenge due to the blood-brain barrier, which protects the brain from toxic substances, but that is not always a good thing.
“Mother Nature designed it to keep us from poisoning ourselves, but unfortunately, the way it works is it prevents about 99% of all small molecule drugs from entering the brain and reaching high enough concentrations to have a therapeutic effect. This is especially true for chemotherapy, biologics, or immunotherapy,” said John Rossmeisl, professor of neurology and neurosurgery at the Virginia-Maryland College of Veterinary Medicine and one of the paper’s co-authors.
The square waves typically used in H-FIRE serve a dual purpose: destroying cancer cells while also disrupting the blood-brain barrier around the tumor site. However, this study was the first to use sine waves to disrupt the barrier. The new technique is called burst sine wave electroporation (B-SWE).
Using a rodent model, the researchers compared the effects of sine waves with traditional square waves and found that B-SWE caused less damage to cells and tissues but more disruption of the blood-brain barrier.
In some clinical cases, both ablation and blood-brain barrier disruption are ideal, whereas in other cases, blood-brain barrier disruption may be more important than destroying cells.
For example, if a neurosurgeon removes a visible tumor mass, they could potentially use the sine wave waveform to disrupt the blood-brain barrier around the tumor site and deliver drugs into the brain to eliminate remaining cancer cells. B-SWE could minimize damage to healthy brain tissue.
Research has shown that while traditional square waves are good at disrupting the blood-brain barrier, this study found that B-SWE can disrupt the blood-brain barrier even better, potentially allowing more anti-cancer drugs to reach the brain.
“We thought that problem was solved, but this just goes to show that if we think ahead, there could always be a better solution,” said Rossmeisl, who also serves as associate director of the department of small animal clinical sciences.
During their studies, the researchers ran into a problem: Not only did the sine waves promote the breakdown of the blood-brain barrier, they also found that they promoted neuromuscular contractions.
These muscle contractions carry the risk of organ damage, but by fine-tuning the dose of B-SWE, the researchers were able to reduce the contractions while still causing the same degree of blood-brain barrier disruption as a higher dose.
The next step in this research is to study the effects of B-SWE using animal models of brain tumors to see how the sinusoidal waveform outperforms traditional H-FIRE techniques.
The project was spearheaded by first author Sabrina Campello, who was completing her PhD at Virginia Tech-Wake Forest University’s School of Biomedical Engineering and Sciences and is currently a postdoctoral researcher in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.
About this Brain Tumor Research News
author: Andrew Mann
sauce: Virginia Tech
contact: Andrew Mann – Virginia Tech
image: Image courtesy of Neuroscience News
Original Research: Open access.
“Burst Sine Wave Electroporation (B-SWE) for Extended 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 Extended 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 penetrate this barrier.
In this study, we introduce burst sine wave electroporation (B-SWE) as a strategic approach to achieve controlled BBB disruption without extensive tissue ablation and compare it with conventional pulsed square wave electroporation-based techniques such as high frequency irreversible electroporation (H-FIRE).
Use In vivo In rodent models, we compare the effects of B-SWE and H-FIRE on BBB disruption, tissue ablation, and neuromuscular contraction.
Comparable waveforms were designed to directly compare the two pulse methods, revealing that B-SWE induces a larger BBB disruption volume while minimizing tissue ablation.
Whereas B-SWE resulted in enhanced neuromuscular contraction compared to the equivalent H-FIRE waveform, an additional low-dose B-SWE group demonstrated that by reducing the voltage, similar levels of BBB disruption could be achieved while minimizing neuromuscular contraction.
The repair kinetics indicated faster closure following B-SWE-induced BBB disruption when compared with a comparable H-FIRE protocol, highlighting the temporary and controllable nature of B-SWE.
Furthermore, finite element modeling demonstrated that while B-SWE can be used to reduce ablation, extensive BBB disruption can occur.
B-SWE is a promising means of achieving customized BBB disruption with minimal tissue ablation, providing a nuanced approach for, for example, the treatment of glioblastoma.
