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

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.

Simulation of the influence of voltage level and pulse spacing on the efficiency, aggressiveness and uniformity of the electroporation process in tissues using meshless techniques

“…Other works in that category include. [39][40][41][42] According to Jiang et al, 34 two other categories of in vitro models to find the irreversible threshold are artificial membrane models, which are simplistic and do not account for the influence of intercellular and intracellular structures on the cell death pathway, [43][44][45][46][47] and single-cell models, which isolate individual cells from their extracellular environment and allow the cell behavior to be studied based on their electric properties. 48 On the other hand, other studies have considered the change in the magnitude of the electric field along the tissue domain and its influence on electric conductivity.…”

“…This particular study can be classified in the category of cell suspension in cuvettes or microfluidic channels, where the membrane or extracellular properties can be modified in a controlled medium, allowing a group of cells under an external electric stimulation to be observed, and the average behavior of the whole cell population can be obtained, whereas the individual cell behavior cannot be characterized. Other works in that category include . According to Jiang et al, two other categories of in vitro models to find the irreversible threshold are artificial membrane models, which are simplistic and do not account for the influence of intercellular and intracellular structures on the cell death pathway, and single‐cell models, which isolate individual cells from their extracellular environment and allow the cell behavior to be studied based on their electric properties …”

Dual-porosity model of mass transport in electroporated biological tissue: Simulations and experimental work for model validation

“…In electroporation, the electric pulses of specific parameters are applied to the target tissue or cell suspension, the parameters depending on the intended goal of application. Often the objectives are to induce a transient increase in cell membrane permeability (Gehl, 2003;Haberl, Miklavcic, Sersa, Frey, & Rubinsky, 2013;Marty et al, 2006;Zorec, Préat, Miklavčič, & Pavšelj, 2013), or to permanently damage and ultimately destroy the cells (Goettel, Eing, Gusbeth, Straessner, & Frey, 2013;Golberg & Yarmush, 2013;Jiang, Qin, & Bischof, 2014;Morales-de la Pena, Elez-Martinez, & Martin-Belloso, 2011;Saulis, 2010). To achieve selective extraction of bio-compounds, complete destruction of the cells is an undesirable effect leading to impure solutions.…”

Irreversible electroporation ablation for atrial fibrillation

“…Yet, despite the extensive number of studies regarding IRE, it remains unclear which levels of electric field, pulse duration, number of pulses, interpulse intervals, and their combinations, are optimal to obtain tissue‐specific death without thermal or limited side effects . Studies performed in vivo used a wide variety of the parameters mentioned above . This variability also affects the preclinical studies regarding interventional electrophysiology, making the comparison between studies a challenging task.…”