Electroporation - Medical Applications

Medical Applications

A higher voltage of electroporation was found in pigs to irreversibly destroy target cells within a narrow range while leaving neighboring cells unaffected, and thus represents a promising new treatment for cancer, heart disease and other disease states that require removal of tissue.

A recent technique called non-thermal irreversible electroporation (N-TIRE) has proven successful in treating many different types of tumors and other unwanted tissue. This procedure is done using small electrodes (about 1mm in diameter), placed either inside or surrounding the target tissue to apply short, repetitive bursts of electricity at a predetermined voltage and frequency. These bursts of electricity increase the resting transmembrane potential (TMP), so that nanopores form in the plasma membrane. When the electricity applied to the tissue is above the electric field threshold of the target tissue, the cells become permanently permeable from the formation of nanopores. As a result, the cells are unable to repair the damage and die due to a loss of homeostasis. N-TIRE is unique to other tumor ablation techniques in that it does not create thermal damage to the tissue around it.

Contrastingly, reversible electroporation occurs when the electricity applied with the electrodes is below the electric field threshold of the target tissue. Because the electricity applied is below the cells’ threshold, it allows the cells to repair their phospholipid bilayer and continue on with their normal cell functions. Reversible electroporation is typically done with treatments that involve getting a drug or gene (or other molecule that is not normally permeable to the cell membrane) into the cell. Not all tissue has the same electric field threshold; therefore careful calculations need to be made prior to a treatment to ensure safety and efficacy.

One major advantage of using N-TIRE is that, when done correctly according to careful calculations, it only affects the target tissue. Proteins, the extracellular matrix, and critical structures such as blood vessels and nerves are all unaffected and left healthy by this treatment. This allows for a quicker recovery, and facilitates a more rapid replacement of dead tumor cells with healthy cells.

The first successful treatment of malignant cutaneous tumors implanted in mice was completed in 2007 by a group of scientists who achieved complete tumor ablation in 12 out of 13 mice. They accomplished this by to sending 80 pulses of 100 microseconds at 0.3Hz with an electrical field magnitude of 2500 V/cm to treat the cutaneous tumors.

Before doing the procedure, scientists must carefully calculate exactly what needs to be done, and treat each patient on an individual case-by-case basis. To do this, imaging technology such as CT scans and MRI’s are commonly used to create a 3D image of the tumor. From this information, they can approximate the volume of the tumor and decide on the best course of action including the insertion site of electrodes, the angle they are inserted in, the voltage needed, and more, using software technology. Often, a CT machine will be used to help with the placement of electrodes during the procedure, particularly when the electrodes are being used to treat tumors in the brain.

The entire procedure is very quick, typically taking about five minutes. The success rate of these procedures is high and is very promising for future treatment in humans. One disadvantage to using N-TIRE is that the electricity delivered from the electrodes can stimulate muscle cells to contract, which could have lethal consequences depending on the situation. Therefore, a paralytic agent must be used when performing the procedure. The paralytic agents that have been used in such research are successful; however, there is always some risk, albeit slight, when using anesthetics.

A more recent technique has been developed called high-frequency irreversible electroporation (H-FIRE). This technique uses electrodes to apply bipolar bursts of electricity at a high frequency, as opposed to unipolar bursts of electricity at a low frequency. This type of procedure has the same tumor ablation success as N-TIRE. However, it has one distinct advantage, H-FIRE does not cause muscle contraction in the patient and therefore there is no need for a paralytic agent.

Scientists have had high success rates in treating lab animals with many different kinds of tumors. Although scientists are not ready to routinely use irreversible electroporation to treat complicated tumors in humans, N-TIRE is more commonly used in humans to treat simple cutaneous or subcutaneous tumors. In addition to treating cutaneous and subcutaneous tumors, there have been attempts at using this technology to treat prostate, lung, kidney and liver cancer in humans. However, scientists are still in the process of understanding this technology and its affect on animals and humans. One study done by Kenneth Thompson et al. tested the safety of N-TIRE on humans suffering from lung, kidney or liver tumors. Of the 69 tumors treated, 49 of them achieved complete tumor ablation. The most successful treatment rate occurred in liver tumors. This study provides encouraging evidence for the future of the use of N-TIRE as a method of treating cancer in humans.

Electroporation can also be used to help deliver drugs or genes into the cell by applying short and intense electric pulses that transiently permeabilize cell membrane, thus allowing transport of molecules otherwise not transported through a cellular membrane. This procedure is referred to as electrochemotherapy when the molecules to be transported is a chemotherapeutic agent or gene electrotransfer when the molecule to be transported is DNA.