Nanopulses tweak the innards of cells

A method that would allow doctors to tweak the innards of cells without even touching a patient's body is being developed in the US.

The technique is still in its infancy, and it is still not clear exactly what it does to cells. But initial experiments suggest it might one day be possible to use the technique to treat cancer, speed up healing or even tackle obesity.

The method involves exposing cells to an extremely powerful electric field for very brief periods. "The effects of these pulses are fairly dramatic," says Tom Vernier of the University of Southern California in Los Angeles, who will present some of his team's results at a nanotechnology conference in Boston in March. "We see it as reaching into the cell and manipulating intracellular structures."

Applying electric pulses to cells is not new. In a technique called electroporation, electric fields that last hundreds of microseconds are applied to cells. The voltage charges the lipid molecules in the cell membrane, creating transient holes in the membrane. The method can be used to help get drugs or genes into cells.

Major physiological event

But the latest technique involves more powerful electric fields, with gradients of tens of megavolts per metre, applied for much shorter periods. These nanosecond-pulsed electric fields are too brief to generate an electric charge across the outer membrane of cells, but they do affect structures within cells.

One of the main effects seems to be calcium release from a cellular structure called the endoplasmic reticulum. "In a nanosecond, we cause this major physiological event in the cell," says Vernier. "It's completely indirect and remote, and it's an extremely rapid transition."

The nanopulses can also trigger cell suicide. Teams led by Vernier, Karl Schoenbach of Old Dominion University and Stephen Beebe of Eastern Virginia Medical School, both in Norfolk, Virginia, have shown that nanopulsing can kill tumour cells in culture.

The pulses do not just fry cells, but lead to changes such as the activation of enzymes called caspases, an early step in cell suicide. How the pulses do this is not clear, but Vernier says the effect is not related to calcium release.

Cell suicide

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So could nanopulsing help treat cancer? In a preliminary test, Schoenbach and Beebe used needle-like electrodes to generate pulses near tumours in mice. Nanopulsing slowed the growth of tumours in four mice by 60 per cent compared with tumour growth in five untreated mice. The researchers hope that with better delivery systems they could make the tumours shrink.

Beebe's team has also found that the pulses can trigger suicide in the cells that give rise to fat cells, possibly opening up a new way of treating obesity, Beebe speculates.

And Vernier is working with doctors at the Cedars-Sinai Medical Center in Los Angeles to see if nanopulses can speed up the healing of wounds. "We do see an effect, but that's about all I can say now," he says.

The next step is to develop a way to deliver the pulses to cells and organs deep within the body. Theoretical models suggest that nanosecond pulses of broadband radio signals could do it. "An array of such antennas would create, through superposition of electric fields, a very high electric field right where we need it," says Schoenbach.

Anil Ananthaswamy