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The Feasibility of Enhancing Susceptibility of Glioblastoma Cells to IRE Using a Calcium Adjuvant

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Abstract

Irreversible electroporation (IRE) is a cellular ablation method used to treat a variety of cancers. IRE works by exposing tissues to pulsed electric fields which cause cell membrane disruption. Cells exposed to lower energies become temporarily permeable while greater energy exposure results in cell death. For IRE to be used safely in the brain, methods are needed to extend the area of ablation without increasing applied voltage, and thus, thermal damage. We present evidence that IRE used with adjuvant calcium (5 mM CaCl2) results in a nearly twofold increase in ablation area in vitro compared to IRE alone. Adjuvant 5 mM CaCl2 induces death in cells reversibly electroporated by IRE, thereby lowering the electric field thresholds required for cell death to nearly half that of IRE alone. The calcium-induced death response of reversibly electroporated cells is confirmed by electrochemotherapy pulses which also induced cell death with calcium but not without. These findings, combined with our numerical modeling, suggest the ability to ablate up to 3.2× larger volumes of tissue in vivo when combining IRE and calcium. The ability to ablate a larger volume with lowered energies would improve the efficacy and safety of IRE therapy.

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Acknowledgments

This work was supported by the NSF Graduate Research Fellowship Program under Grant No. DGE-1651272, the National Cancer Institute of the National Institutes of Health under Award R01CA213423, the Institute for Critical Technology and Applied Science (ICTAS) of Virginia Tech, Wake Forest Comprehensive Cancer Center and NSF CAREER Awards CBET-1055913 and CBET-1652112.

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Authors and Affiliations

  1. Department of Mechanical Engineering, Virginia Tech, Goodwin Hall, 635 Prices Fork Road – MC 0238, Blacksburg, VA, 24061, USA

    Elisa M. Wasson & Rafael V. Davalos

  2. Department of Biomedical Engineering and Mechanics, Virginia Tech, 325 Stanger Street, Blacksburg, VA, 24061, USA

    Jill W. Ivey, Scott S. Verbridge & Rafael V. Davalos

  3. Virginia Tech – Wake Forest University, School of Biomedical Engineering & Sciences, Virginia Tech, 325 Stanger St., Blacksburg, VA, 24061, USA

    Jill W. Ivey, Scott S. Verbridge & Rafael V. Davalos

  4. Bioelectromechanical Systems Laboratory, Department of Biomedical Engineering and Mechanics, Virginia Tech – Wake Forest University, School of Biomedical Engineering & Sciences, 325 Stanger St., Blacksburg, VA, 24061, USA

    Elisa M. Wasson & Rafael V. Davalos

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  1. Elisa M. Wasson
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Correspondence to Elisa M. Wasson.

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Associate Editor Dan Elson oversaw the review of this article.

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Wasson, E.M., Ivey, J.W., Verbridge, S.S. et al. The Feasibility of Enhancing Susceptibility of Glioblastoma Cells to IRE Using a Calcium Adjuvant. Ann Biomed Eng 45, 2535–2547 (2017). https://doi.org/10.1007/s10439-017-1905-6

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  • DOI: https://doi.org/10.1007/s10439-017-1905-6

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