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Membrane-Targeting Approaches for Enhanced Cancer Cell Destruction with Irreversible Electroporation

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Abstract

Irreversible electroporation (IRE) is a promising technology to treat local malignant cancer using short, high-voltage electric pulses. Unfortunately, in vivo studies show that IRE suffers from an inability to destroy large volumes of cancer tissue without introduction of cytotoxic agents and/or increasing the applied electrical dose to dangerous levels. This research will address this limitation by leveraging membrane-targeting mechanisms that increase lethal membrane permeabilization. Methods that directly modify membrane properties or change the pulse delivery timing are proposed that do not rely on cytotoxic agents. This work shows that significant enhancement (67–75% more cell destruction in vitro and >100% treatment volume increase in vivo) can be achieved using membrane-targeting approaches for IRE cancer destruction. The methods introduced are surfactants (i.e., DMSO) and pulse timing which are low cost, non-toxic, and easy to be incorporated into existing clinical use. Moreover, when needed, these methods can also be combined with electrochemotherapy to further enhance IRE treatment efficacy.

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Notes

  1. We chose to use 51 pulses in the pulse timing method so that the same number of pulses (17) can be delivered in each train. The dose difference between 51 and 50 pulses in our baseline groups is marginal.

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Acknowledgments

This study was supported by Ethicon Endo-Surgery Inc. We thank Peter Shires for helpful discussions. JCB was supported by a McKnight Distinguished Professorship and the Carl and Janet Kuhrmeyer Chair of Mechanical Engineering from the University of Minnesota.

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Authors and Affiliations

  1. Department of Mechanical Engineering, University of Minnesota, 111 Church St. SE, Minneapolis, MN, 55455, USA

    Chunlan Jiang & John Bischof

  2. Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, USA

    Zhenpeng Qin & John Bischof

  3. Department of Urological Surgery, University of Minnesota, Minneapolis, MN, USA

    John Bischof

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  1. Chunlan Jiang
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  2. Zhenpeng Qin
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  3. John Bischof
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Correspondence to John Bischof.

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Associate Editor Cheng Dong oversaw the review of this article.

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Jiang, C., Qin, Z. & Bischof, J. Membrane-Targeting Approaches for Enhanced Cancer Cell Destruction with Irreversible Electroporation. Ann Biomed Eng 42, 193–204 (2014). https://doi.org/10.1007/s10439-013-0882-7

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