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Electroporation-induced electrosensitization.

Olga N Pakhomova1, Betsy W Gregory, Vera A Khorokhorina

  • 1Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, Virginia, United States of America.

Plos One
|February 25, 2011
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Summary

Electric pulses (EPs) sensitize cells to subsequent EPs, increasing treatment efficiency. This cell sensitization effect can be leveraged to enhance electroporation applications or mitigate side effects in therapies.

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Area of Science:

  • Biophysics
  • Cell Biology
  • Biotechnology

Background:

  • Electroporation uses electric pulses (EPs) to disrupt cell membranes.
  • Current electrical models of electroporation have limited predictive power.
  • The biological consequences of electroporation on cell susceptibility are not well understood.

Purpose of the Study:

  • To investigate the role of electric pulse (EP) rate on cell membrane permeabilization and cell death.
  • To determine if biological consequences of electroporation alter cell susceptibility to subsequent EPs.
  • To explore how EP rate and exposure duration affect electroporation efficiency.

Main Methods:

  • Varied EP rates (0.001–2,000 Hz) with constant pulse parameters (duration, number, amplitude).
  • Assessed membrane permeabilization and lethal effects in mammalian cells.
  • Investigated the impact of exposure duration and delayed fractionation of EP trains.

Main Results:

  • EP treatment efficiency was minimal at high EP rates and increased as rates decreased below a threshold (0.1–500 Hz), correlating with ~10s total duration.
  • Longer exposure durations consistently enhanced electroporation efficiency.
  • Splitting EP trains with a 1-5 minute delay significantly increased treatment effects.

Conclusions:

  • Electric pulses induce a delayed, gradual sensitization in cells, increasing susceptibility to subsequent EPs.
  • This sensitization can markedly enhance treatment outcomes, allowing for reduced exposure dose or increased cell lethality.
  • Accounting for sensitization can optimize electroporation applications like sterilization and reduce side effects in therapies such as electrochemotherapy and gene therapy.