Researchers at the Georgia Institute of Technology and Emory University in Atlanta this week released findings relating to how ultrasound energy is able to see through the protective outer membranes of living cells to ease the entry of drugs and other therapeutic molecules. Ultrasound energy also reveals how the cells themselves quickly close back up. The researchers hope that this information proves useful in advancing ultrasound use for delivering gene therapies, targeting chemotherapy, and administering large-molecule drugs that cannot readily move through cell membranes, according to a release of the findings.
The researchers used five microscopy techniques to show that ultrasound produces an effect that enables holes to open in the membranes of cells suspended in a liquid medium. The holes allow entry of therapeutic molecules as large as 50 nanometers in diameter -- larger than most proteins and similar in size to the DNA used for gene therapy. The holes are closed by the cells within minutes.
"The holes are made by mechanical interaction with the collapsing bubbles," said Mark Prausnitz, a professor in the School of Chemical and Biomolecular Engineering at the Georgia Institute of Technology. "The bubbles oscillate in the ultrasound field and collapse, causing a shock wave to be released. Fluid movement associated with the resulting shock wave opens holes in the cell membranes, which allow molecules from the outside to enter. The cells then respond to the creation of the holes by mobilizing intracellular vesicles to patch the holes within minutes."
Ultrasound drug delivery could be particularly attractive for gene therapy, which has successfully used viruses to insert genetic material into cells — but with side effects. It also could be used for more targeted delivery of chemotherapy agents.
"One of the great benefits of ultrasound is that it is noninvasive," Prausnitz said. "You could give a chemotherapeutic drug locally or throughout the body, then focus the ultrasound only on areas where tumors exist. That would increase the cell permeability and drug uptake only in the targeted cells and avoid affecting healthy cells elsewhere." Researchers have only recently found that the application of ultrasound can help move drugs into cells by increasing the permeability of cell membranes. It had been hypothesized, but not definitively shown, that the ultrasound increased the permeability by opening holes in cell membranes,” he added.
The research was first reported in the journal Ultrasound in Medicine and Biology (Vol. 32, No. 6) and supported by the National Institutes of Health and the National Science Foundation.