Ultrasound Activates Nanoparticle Drug Delivery

Targeted nanoparticles, which bind to molecules found only on the surfaces of tumor cells, have shown remarkable potential for increasing the effectiveness of anticancer agents while decreasing their possible side effects. Now, investigators at Washington University School of Medicine (St. Louis, MO, USA) have taken targeting one step further by using ultrasound to increase the efficiency with which the targeted nanoparticles deliver drugs into cells.

Publishing their study in the December 2005 issue of the journal Ultrasound in Medicine & Biology, a group led by Samuel Wickline, M.D., director of the Siteman Center of Cancer Nanotechnology Excellence at Washington University, and Gregory Lanza, M.D., performed studies utilizing the liquid perfluorocarbon nanoparticles, which they have been developing as targeted cancer drug delivery agents over the past several years. At least one such compound is being planned to start human clinical trials within the next year or so. The researchers also used commercially available diagnostic ultrasound equipment, the same equipment that obstetricians currently use to generate sonograms of a developing fetus, to generate focused ultrasonic energy designed to enhance drug delivery.

In this study, the nanoparticles were constructed to display a molecule that binds specifically to a protein known as alpha-beta-v3, which is found on the surface of specific types of cancer cells, including melanoma cells. The investigators loaded the nanoparticles with a fluorescent dye, instead of an anticancer drug, to follow the outcome of the nanoparticles and their cargo when combined with melanoma cells growing in culture.

After mixing the nanoparticles with cultured melanoma cells, the investigators applied ultrasonic energy for five minutes. Using a fluorescence microscope, the researchers noted that the cells subjected to ultrasound took up about 10 times more of the fluorescent dye than when no ultrasound is applied. The investigators captured images of the dye streaming into the cell's plasma membrane and then into the cytoplasm. Control tests using ultrasound energy and no nanoparticles demonstrated that cells were not damaged by the application of ultrasonic energy for five minutes.

The researchers observed that these findings supported the theory that ultrasound augments the exchange of molecules between the fat-soluble nanoparticle components and the lipids that comprise the cell membrane. They also commented in their study that enhanced, nanoparticle-aided drug delivery using widely available ultrasound equipment could greatly improve the safety of cancer therapy while reducing the amount of drug used and lowering the cost of therapy.




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