Electrotransfer: What It Is and Its Key Applications

Electrotransfer is a method that allows scientists and medical professionals to introduce substances directly into living cells. It uses controlled electrical pulses to create temporary openings in the cell membrane, which normally acts as a selective barrier. This technique has enabled a wide range of uses in laboratory research and clinical medicine for modifying cellular function.

The Process of Electrotransfer

Every cell is enclosed by a plasma membrane that regulates the passage of substances. Electrotransfer works by temporarily overcoming this natural barrier. The process begins when cells are suspended in a conductive solution and placed between two electrodes.

An applied electrical pulse creates an external electric field, inducing a voltage difference across the membrane. If this voltage surpasses a certain threshold, between 200 millivolts and 1 volt, it causes a rapid and localized rearrangement of the membrane’s lipid molecules.

This structural disturbance forms temporary, water-filled channels known as electropores. These nanometer-sized pores act as pathways through which molecules in the surrounding fluid can move into the cell. Once the electrical pulse ceases, the cell membrane quickly reseals, trapping the delivered molecules inside and allowing the cell to return to its normal state.

Molecules Delivered via Electrotransfer

The versatility of electrotransfer is demonstrated by the wide array of molecules that can be delivered into cells. A primary category is nucleic acids, including plasmid DNA for long-term protein production and various forms of RNA. Messenger RNA (mRNA) can be used for temporary protein expression, while small interfering RNA (siRNA) can silence specific genes, allowing for direct manipulation of a cell’s genetic activity.

Electrotransfer is also a method for delivering drugs that have difficulty crossing cell membranes on their own. Certain chemotherapeutic agents, such as bleomycin and cisplatin, have low membrane permeability but are effective once inside a cell. The technique can increase the intracellular concentration of these drugs, enhancing their cytotoxic effects on target cells.

The technique is also capable of introducing larger molecules like proteins. Functional proteins such as antibodies or enzymes can be delivered into the cytoplasm to study or alter cellular processes. Additionally, smaller molecules like fluorescent dyes can be introduced to label and track cells for research purposes.

Major Fields of Application

One of the most prominent clinical uses for electrotransfer is in cancer treatment through a procedure called electrochemotherapy. In this application, a low-permeability chemotherapy drug is administered, and electrical pulses are then applied directly to a tumor. This localizes the drug’s entry into cancer cells, increasing its effectiveness while minimizing exposure to healthy tissues and reducing side effects.

Gene therapy is another area of application. The method is used to deliver therapeutic genes into target tissues to treat diseases rooted in genetic mutations. For example, a functional copy of a gene can be delivered to muscle cells to correct a disorder. This can be performed in vivo, with the gene delivered directly into the patient, or ex vivo, where cells are removed, treated, and then returned.

Electrotransfer is also advancing the development of new vaccines. DNA and RNA vaccines use genetic material to prompt an immune response and rely on efficient delivery into host cells. Applying electrical pulses at the site of injection enhances the uptake of vaccine plasmids by muscle or skin cells, which then produce the specified antigen and activate the immune system.

In biomedical research, it remains a foundational technique for creating genetically modified cells to study gene function and for producing proteins of interest.

Parameters and Optimization

The success of electrotransfer depends on the careful control and optimization of several parameters. The characteristics of the electrical pulse are a primary consideration, including the electric field strength (voltage), pulse duration, and the number of pulses applied. Higher voltages and longer pulses can create larger pores but also increase the risk of irreversible cell damage.

The properties of the cells being targeted are also a factor, as different cell types respond differently to the same electrical parameters. Key cellular properties include:

• Cell size and shape
• Membrane composition
• The cell’s physiological state
• The cell’s stage in the cell cycle

The composition of the solution, or buffer, in which the cells are suspended is an important variable. The buffer’s ionic strength and conductivity can alter how the electric field is distributed. The characteristics of the molecule being delivered, such as its size, concentration, and electrical charge, also dictate the optimal pulse settings.