ID: 2176

• Title:
  Effects of different nanosecond pulsed electric fields (nsPEF) parameters on multicellular colorectal carcinoma spheroids
  
  Authors:
  

  Orlacchio, Rosa,IMS/EPHE, France
  Kolosnjaj-Tabi,Jelena,IPBS,France
  Mattei, Nicolas, IPBS, France 
  Leveque, Philippe  XLIM, France
  Rols, Marie Pierre, IPBS, France
  Golzio, Muriel, IPBS, France
  Arnaud-Cormos, Delia, IUF/XLIM, France
  
  
  InsDtut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, 31077 Toulouse, France
  4Univ. Limoges, CNRS, XLIM, UMR 7252 F-87000 Limoges, France
  5InsDtut Universitaire de France (I

  
  
  Abstract:
  The use of high-intensity (tens of MV/m) nanosecond pulsed electric fields (nsPEF) is emerging as a minimally
  
  invasive and highly localized cancer treatment modality [1]. The unique capability of nsPEF to bypass cell plasma membrane supports specific intracellular responses including the activation of regulated cell death and the initiation of an adaptive immune response [2], [3]. Numerous studies, within in vitro and in vivo models, have demonstrated the efficacy of nsPEF against several cancers, including melanoma [4], breast [5], or prostate cancer [6], among others, mostly using PEF with durations of hundreds of ns.
  
  We have recently demonstrated that trains of at least 100 unipolar electric pulses of 10 ns (5 MV/m at 20 Hz) can trigger cellular mortality of 3D multicellular spheroids derived from colorectal carcinoma cells [7], suggesting that
  
  nsPEF < 100 ns are excellent candidates for non-invasive and selective targeting of tumors.
  
  Cellular response to PEF simulation results from a combination of different pulse parameters, such as number,
  
  duration, the intensity of the electric field, pulse repetition rate (PRR), pulsing buffer conductivity, electrical dose, etc.
  
  Therefore, a deep insight into the impact of such parameters on cellular response is paramount to adaptively optimize and target the lethal effect of the treatment. Thus, in this study, we extended our previous results [7],
  
  exploring the potential effects of nsPEF ≤ 10 ns on long-term cellular viability and growth as a function of the 1)
  
  duration (2 – 10 ns), 2) PRR (20 and 200 Hz), 3) cumulative dose (1 – 5 microseconds), and 4) pulsing buffer
  
  conductivity (0.2 – 1.4 S/m).
  
  A commercial generator (FID Technology) was used to deliver unipolar pulses of approximately 2, 4, 6, 8, and 10
  
  ns with a bias voltage of 10 kV through a pair of steel electrodes. Fluorescence microscopy was used to investigate
  
  live cell spheroid viability and growth following propidium iodide uptake over a period of 6 days post-exposure [7]. nsPEF-induced temperature elevation in the pulsing buffer was measured through a fiber-optic probe.
  
  Our results show that all applied pulse parameters play an important role in the outcome of the cellular response.
  
  In particular, the use of a high buffer conductivity resulted in a more prominent cell death compared to cells exposed in a low conductivity buffer.
  
  Detailed results will be presented and further discussed at the conference.
  
  
  
  
  
  Keywords:
  nanosecond pulsed electric field (nsPEF), cancer ablation, 3D cells, multicellular spheroids
  
  Refs:
  References [1] R. Nuccitelli, Chapter 94, in Handbook of Electropora1on. Springer, 2016. [2] S. Beebe, Chapter 9, in Ultrashort Electric Pulse Effects in Biology and Medicine, Springer, 2021. [3] S. Beebe, Chapter 19, in Ultrashort Electric Pulse Effects in Biology and Medicine, Springer, 2021. [4] R. Nuccitelli et al., Biochem. Biophys. Res. Commun., 343(2), 351–360, 2006. [5] S. Beebe et al., 10(4), 97, 2018. [6] A. Kie?bik et al., Sci. Rep., 11(1), 2021. [7] L. Carr et al., Bioelectrochemistry, 141, 107839, 2021.
  
  Topic 1:
  1. Biological responses (molecular, subcellular, cellular and intercellular)
  
  Topic 2:
  6. Cancer treatment and tumor ablation