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Towards solid tumor treatment by nanosecond pulsed electric fields.

Alex T Esser1, Kyle C Smith, T R Gowrishankar

  • 1Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology Cambridge MA 02139, USA.

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Large nanosecond pulsed electric fields ablate solid tumors via supra-electroporation, inducing apoptosis. This non-thermal mechanism involves nanometer-sized pores affecting ion transport, not larger molecules, for effective tumor ablation.

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Area of Science:

  • Biophysics
  • Biomedical Engineering
  • Oncology

Background:

  • Solid tumor ablation is a critical challenge in oncology.
  • Nanosecond pulsed electric fields (nsPEFs) offer a drug-free approach for tumor treatment.
  • Previous studies suggest nsPEFs induce apoptosis, but the precise mechanism requires elucidation.

Purpose of the Study:

  • To investigate the pore-based mechanisms underlying apoptosis induction by nsPEFs in solid tumors.
  • To differentiate the effects of nsPEFs from longer irreversible electroporation pulses.
  • To establish the role of non-thermal electrical interactions in nsPEF-induced cell death.

Main Methods:

  • Utilized a multicellular system model of irregularly shaped liver cells (100 microm spatial scale).
  • Employed a multiscale liver tissue model (200 mm spatial scale).
  • Analyzed pore formation and histograms, tissue conductance, and membrane permeability to ions and molecules.

Main Results:

  • nsPEFs create nanometer-sized pores in cellular membranes, distinct from longer electroporation pulses.
  • Increased numbers of nanometer pores lead to higher tissue conductance during nsPEF application.
  • Membrane permeability is significantly altered for small ions but not for larger molecules.

Conclusions:

  • The primary mechanism for nsPEF-induced apoptosis in solid tumors is non-thermal, driven by electrical interactions.
  • Nanometer-sized pores generated by nsPEFs facilitate specific ionic transport, contributing to tumor ablation.
  • These findings differentiate nsPEF effects from conventional electroporation, highlighting a novel therapeutic modality.