期刊
SCIENTIFIC REPORTS
卷 5, 期 -, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/srep17157
关键词
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资金
- NSF-REU program in Multiscale Biomechanics (EEC Award) [1359073]
- NSF CAREER Award [CBET-1055913]
- R21 Award from the National Cancer Institute of the National Institutes of Health [R21CA192042]
- ISBET center of the Institute of Critical Technology and Applied Science at Virginia Tech
- MBEDS center of the Institute of Critical Technology and Applied Science at Virginia Tech
- Directorate For Engineering
- Div Of Engineering Education and Centers [1359073] Funding Source: National Science Foundation
Treatment of glioblastoma multiforme (GBM) is especially challenging due to a shortage of methods to preferentially target diffuse infiltrative cells, and therapy-resistant glioma stem cell populations. Here we report a physical treatment method based on electrical disruption of cells, whose action depends strongly on cellular morphology. Interestingly, numerical modeling suggests that while outer lipid bilayer disruption induced by long pulses (similar to 100 mu s) is enhanced for larger cells, short pulses (similar to 1 mu s) preferentially result in high fields within the cell interior, which scale in magnitude with nucleus size. Because enlarged nuclei represent a reliable indicator of malignancy, this suggested a means of preferentially targeting malignant cells. While we demonstrate killing of both normal and malignant cells using pulsed electric fields (PEFs) to treat spontaneous canine GBM, we proposed that properly tuned PEFs might provide targeted ablation based on nuclear size. Using 3D hydrogel models of normal and malignant brain tissues, which permit high-resolution interrogation during treatment testing, we confirmed that PEFs could be tuned to preferentially kill cancerous cells. Finally, we estimated the nuclear envelope electric potential disruption needed for cell death from PEFs. Our results may be useful in safely targeting the therapy-resistant cell niches that cause recurrence of GBM tumors.
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