Optimizing pulsed electric fields to target cancer with calcium ionsSeveral different treatment methods are used against cancer and multiple promising approaches are currently under examination by various institutions around the world. In Japan, one method in particular, calcium electrotransfer, is being studied at Kumamoto University’s Institute of Pulsed Power Science.
Pulsed electric fields (PEFs) have multiple applications in biology, ranging from DNA/drug delivery to the elimination of microorganisms in water. Their use against cancer is not new, but their basic effects on cells are still being clarified. Researchers at Kumamoto University’s Bioelectrics Department recently identified the optimal PEF conditions for increasing the permeability of a cell membrane to calcium. This technique is appealing as a potential cancer treatment since cancer cells are particularly sensitive to an abnormal influx of calcium, it is comparatively cheap, and it has few side effects.
The researchers examined calcium intake in HeLa S3 cells via calcium (Ca2+) fluorescence. For each test, they used a fixed amount of energy but changed the PEF pulse count to assess the effects of electric field changes rather than that of total energy. Researchers found that membrane permeability continues for a short while after PEF is terminated because it takes time for the pores in the membrane to completely close. This gives a little more time for CA2+ to diffuse into the cells.
Of the four electric fields examined, the two larger fields (1.8 and 1.26 kV/cm) produced a high CA2+ intake rate during the first 10 ms that decreased significantly thereafter. On the other hand, the intake rate during the first 10 ms for the two smaller fields (0.63 and 0.45 kV/cm) was undetectable and gradually increased afterward. The rates for these two fields were very similar to one another until the end of the analysis.
“The optimal PEF levels for our in-vitro tests turned out to be 100 pulses at 1 kHz and 0.45 kV/cm,” said study leader Dr. Hamid Hosseini. “This setting should be nonlethal to normal cells but effectively kill cancer cells. We still have more work to determine if these results will hold up in in-vivo settings, but we are optimistic that this method can produce a promising cancer therapy.”
This research was published online in the journal Drug Delivery and Translational Research on 11 May 2018.
Guionet, A., Moosavi Nejad, S., Teissié, J., Sakugawa, T., Katsuki, S., Akiyama, H., & Hosseini, H. (2018). Spatio-temporal dynamics of calcium electrotransfer during cell membrane permeabilization. Drug Delivery and Translational Research. doi:10.1007/s13346-018-0533-5
Fluorescent images of the uptake of extracellular calcium through the cell membrane.
Sample fluorescence images at 50 ms for 0.27 kV/cm to 1.8 kV/cm electric fields. The ground (negative cathode) is at the left and the high voltage (positive anode) is at the right side. (Scale bars: 100 μm)
Reprinted by permission from Springer Customer Service Centre GmbH: Springer Nature, Drug Delivery and Translational Research, Spatio-temporal dynamics of calcium electrotransfer during cell membrane permeabilization, Guionet, A., Moosavi Nejad, S., Teissié, J., Sakugawa, T., Katsuki, S., Akiyama, H., & Hosseini, H, 2018.
CREDIT: Dr. Hamid Hosseini
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Support in part by Grant-in-Aid for Scientific Research (Kakenhi) from MEXT Japan