Burst sine wave electroporation has been found to cause less harm to cells and tissues but more disruption to the blood-brain barrier.
Dealing with brain cancer is complex, but a recent groundbreaking study may introduce a new weapon in the fight against cancer.
A joint team from Georgia Tech and Virginia Tech recently published a study in APL Bioengineering in May focusing on a potential new method that could target glioblastoma, a rapidly growing and lethal brain tumor.
Funded by grants from the National Institutes of Health, this research builds upon previous studies on high frequency irreversible electroporation, referred to as H-FIRE. This minimally invasive technique utilizes non-thermal electrical pulses to break down cancer cells.
Treating any form of cancer is challenging, but when it comes to brain tumors, the presence of the blood-brain barrier adds an additional layer of complexity. While the barrier shields the brain from harmful substances, it can hinder the effectiveness of certain treatments.
“Mother Nature intended it to protect us from poisoning ourselves, but unfortunately, it also prevents about 99% of small-molecule drugs from reaching the brain in adequate amounts to produce therapeutic effects. This is especially true for chemotherapeutic agents, biologics, or immunotherapies,” explained John Rossmeisl, the Dr. and Mrs. Dorsey Taylor Mahin Endowed Chair of Neurology and Neurosurgery at the Virginia-Maryland College of Veterinary Medicine and a coauthor of the study.
The conventional square wave used in H-FIRE has a dual benefit: it disrupts the blood-brain barrier around the tumor site while destroying cancer cells. However, this particular study introduced a novel approach by employing a burst sine wave to disrupt the barrier, termed burst sine wave electroporation (B-SWE).
Through experiments on a rodent model, the researchers compared the effects of the sine wave versus the traditional square wave. They observed that B-SWE resulted in less cellular and tissue damage but more disruption of the blood-brain barrier.
In certain clinical scenarios, a combination of tissue ablation and blood-brain barrier disruption would be ideal, while in others, disrupting the barrier could be more crucial than cell destruction. For instance, after a neurosurgeon removes the visible tumor mass, the sine wave could potentially be used to disrupt the blood-brain barrier surrounding the area, facilitating drug penetration into the brain to eradicate any remaining cancer cells. B-SWE could achieve this with minimal impact on healthy brain tissue.
Prior evidence suggests that the standard square waveforms are effective in disrupting the blood-brain barrier, but this research demonstrates even greater barrier disruption with B-SWE. This could improve the delivery of cancer-fighting medications to the brain.
“We thought we had addressed that challenge, but this demonstrates that with forward-thinking, there may be even better solutions available,” remarked Rossmeisl, who also serves as the associate head of the Department of Small Animal Clinical Sciences.
During the study, the researchers encountered an obstacle: apart from increased blood-brain barrier disruption, the sine wave also induced more neuromuscular contractions, which could potentially harm the organ. However, by adjusting the B-SWE dosage, they managed to reduce the contractions while maintaining a level of barrier disruption similar to a higher dose.
The next phase of the research involves assessing the effects of B-SWE using an animal model of brain cancer to compare it against the conventional H-FIRE technique.
The study was led by Sabrina Campelo, the primary author who conducted this research during her Ph.D. studies at the Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences. Campelo is currently a postdoctoral fellow at the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.
