Nanoelectroablation: A Revolutionary Cancer Therapy Nanoelectroablation is a completely new approach to treating tumors that triggers apoptosis, the tumor cell’s own programmed cell death pathway. Once triggered, the tumor slowly shrinks and is scavenged by the immune system, initiating an innate immune response that attacks other tumors in mice, writes Dr Richard Nuccitelli of BioElectroMed Corp Electrical pulse technology has been applied to living cells since the 1970’s and was first used to generate transient increases in the permeability of a cell’s plasma membrane, a technique called electroporation. Researchers continue to investigate the capacity of electric fields to modify cells, with a particular focus at BioElectroMed on how the electrical properties of tissues can be utilized to detect and treat disease.
These nanosecond pulsed electric fields (nsPEFs) have profound effects on treated cells, with their most important characteristic being their ability to penetrate into the cell cytoplasm to
Unique Mechanism
Electric fields When electric fields on the order of 1 volt are applied across a biological membrane they cause a breakdown in the lipid bilayer of the cell’s plasma membrane. This results in a water-filled pathway across the lipid membrane that allows ions and other small molecules to cross the normally impermeable lipid bilayer. Early studies in this area used pulsed electric fields in the microsecond and millisecond time domains, with field strengths on the order of 1 kV/cm. It was found that the pores that formed in cell membranes were transient and reversible unless the field strength was increased to 2-3 kV/cm, in which case irreversible pores were formed that killed cells by necrosis, where cell death is caused by the influx of external factors such as calcium ions. It is now possible to apply much shorter electrical pulses than those used in electroporation, which opens up new possibilities in treatment. These shorter pulses, in the nanosecond time domain with electric field strengths of between 10-100 kV/cm, also introduce transient, water-filled defects across the plasma membrane. However, only molecules with a diameter less than 1 nanometre (nm) can cross the membrane through these transient nanopore pathways.
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permeabilize organelle membranes as well as the plasma membrane [1]. BioElectroMed is developing novel bioelectric approaches based on low energy, non-thermal, nsPEFs which penetrate into every cell and trigger apoptosis, the cell’s own programmed cell death pathway.
Figure 1. Melanoma treated on day 0 with 2000 pulses 30 kV/cm, 100 ns long. Left column shows transillumination image of tumor beneath nude mouse skin taken on the day after nsPEF treatment indicated in upper left of photo. Right column shows the reflected light image of the skin above the melanoma taken on the same day. The scale bar on the upper left applies to all images.
All cells are bound by an outer plasma membrane, normally composed of a lipid bilayer with associated glycoproteins, which exhibits very low conductivity in comparison to the cytoplasm and extracellular fluid. This means the cell can be modelled as a conductor surrounded by an insulating layer, as is also generally true for organelles within the cytoplasm of cells. When an electric field is imposed across a cell, ions in the cytoplasm respond by rapidly moving in the field direction to charge the capacitance of the membrane until they experience no further force. By definition, this will only occur when their redistribution establishes an equal and opposite field so that the net field in the cell interior is zero. The duration of this redistribution is characterized by the charging time constant of the membrane, which is typically in the 0.1-1 microsecond (µs) range. Nanosecond pulsed electric fields (nsPEFs) are much faster than that so they penetrate into the cell before the charged molecules can redistribute to counteract the field. Once inside the cell, this field can generate nanopores in all organelle membranes if the field is large enough. This ability to penetrate into the cytoplasm allows nsPEFs to permeabilize the organelle membranes as well as the plasma membrane, which is one of the
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