Summary: Researchers have developed a new method, burst sinusoidal electroporation (B-SWE), to treat glioblastoma, a fast-growing brain tumor. B-SWE disrupts the blood-brain barrier more effectively than traditional methods, allowing anticancer drugs to more easily access the brain.
This technique could improve treatment by minimizing damage to healthy brain tissue while targeting cancer cells. The study highlights a promising advance in the treatment of brain cancer.
Highlights:
- B-SWE disrupts the blood-brain barrier more effectively than conventional methods.
- This technique could allow more anti-cancer drugs to enter the brain.
- B-SWE minimizes damage to healthy brain tissue while targeting cancer cells.
Source: Virginia Tech University
Fighting brain cancer is a complex task, 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, which is exploring a new option that could one day be used to target glioblastoma, a deadly, fast-growing brain tumor.
Supported by grants from the National Institutes of Health, this work builds on previous 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.
Treating any cancer is not easy, but when it comes to brain cancers, the blood-brain barrier presents an additional challenge. This barrier protects the brain from toxic substances, but that’s not always a good thing.
“Mother Nature designed this system to prevent us from poisoning ourselves, but unfortunately, about 99 percent of small molecule drugs cannot get into the brain and reach concentrations sufficient to elucidate their therapeutic effect this way. This is especially true for chemotherapies, biologics or immunotherapies,” said John Rossmeisl, professor of neurology and neurosurgery at the Virginia-Maryland College of Veterinary Medicine. Rossmeisl is a co-author of the study.
The square wave typically used with H-FIRE serves a dual purpose: it disrupts the blood-brain barrier around the tumor site while destroying cancer cells. However, this was the first study to use a sine 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 sine wave versus the more conventional square wave. They found that the B-SWE wave caused less damage to cells and tissues, but more disruption to the blood-brain barrier.
In some clinical cases, ablation and disruption of the blood-brain barrier would be ideal, but in other cases, disruption of the blood-brain barrier may be more important than cell destruction.
For example, if a neurosurgeon removes 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 remaining cancer cells. B-SWE could result in minimal damage to healthy brain tissue.
Research indicates that conventional square waveforms have good blood-brain barrier disruption, but this study reveals even better blood-brain barrier disruption with B-SWE. This could allow more anti-cancer drugs to access the brain.
“We thought we had solved this problem, but it shows that with a little forward thinking, there are always potentially better solutions,” said Rossmeisl, who is also deputy director of the department of small animal clinical sciences.
During the study, the researchers encountered a problem: In addition to greater disruption of the blood-brain barrier, they found that the sine wave also caused more neuromuscular contractions.
These muscle contractions have the potential to damage the organ. However, by slightly changing the dose of B-SWE, they were able to reduce the contractions while causing a similar level of blood-brain barrier disruption as 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 holds up to the conventional H-FIRE technique.
The project was led by first author Sabrina Campelo while she was completing her doctorate at the Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences. Campelo is now a postdoctoral researcher in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.
About this brain cancer research news
Author: André Mann
Source: Virginia Tech University
Contact: Andrew Mann – University of Virginia
Picture: Image credited to Neuroscience News
Original research: Free access.
“Burst Sine Wave Electroporation (B-SWE) for Expansive Blood-Brain Barrier Disruption and Controlled Non-Thermal Tissue Ablation for Neurological Diseases” 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 Diseases
The blood-brain barrier (BBB) limits the effectiveness of treatments for malignant brain tumors, requiring innovative approaches to cross the barrier.
This study presents burst sine wave electroporation (B-SWE) as a strategic modality for controlled BBB disruption without extensive tissue ablation and compares it to conventional pulsed square wave electroporation-based technologies such as high-frequency irreversible electroporation (H-FIRE).
Use a alive rodent model, the effects of B-SWE and H-FIRE on BBB disruption, tissue ablation and neuromuscular contractions are compared.
Equivalent waveforms were designed for direct comparison between the two pulse patterns, revealing that B-SWE induces larger BBB disruption volumes while minimizing tissue ablation.
While B-SWE exhibited increased neuromuscular contractions compared to equivalent H-FIRE waveforms, an additional low-dose B-SWE group demonstrated that reduced potential can achieve similar levels of BBB disruption while minimizing neuromuscular contractions.
Repair kinetics indicated faster closure after BBB disruption induced by B-SWE compared to equivalent H-FIRE protocols, highlighting the transient and controllable nature of B-SWE.
Additionally, finite element modeling illustrated the potential for extensive BBB disruption while reducing ablation using B-SWE.
B-SWE presents a promising avenue for personalized BBB disruption with minimal tissue ablation, offering a nuanced approach for the treatment of glioblastoma and beyond.