June 12, 2006
Acoustic Nanoparticles Deliver Drug without Damaging Cells
Targeted nanoparticles made of liquid perfluorocarbons are well on the way to human clinical trials as both imaging agents and sound-activated drug delivery vehicles for detecting and treating cancer. A new report published in the journal IEEE Transactions on Nanobioscience presents data showing that acoustic activation of these nanoparticles does not damage cells, unlike acoustically generated microbubbles.
In the current study, a team led by Samuel Wickline, M.D., and Gregory Lanza, M.D., both members of the Siteman Center of Cancer Nanotechnology Excellence at Washington University who have been developing these nanoparticles with funding from the National Cancer Institute that began in 2000, wanted to test the hypothesis that perfluorocarbon nanoparticles do not act as “cavitation nuclei,” which are sites at which ultrasound triggers the formation of microbubbles. When microbubbles generated in this manner burst, they release energy that can damage cells.
The investigators tested this hypothesis using human umbilical vein endothelial cells grown into a monolayer on an inert membrane. They treated these cells with ultrasound, ultrasound plus a commercial ultrasound contrast agent, and ultrasound plus perfluorocarbon nanoparticles. Treatment with ultrasound alone or with the perfluorocarbon nanoparticles had no effect on the cultured cells, even after five minutes of ultrasound treatment. However, continuous ultrasound in the presence of the commercial contrast agent had a marked effect on cells, including a reduction in cell viability of nearly 50 percent and physical disruption of the cell monolayer.
Previous studies by these investigators (click here for earlier story) had already shown that ultrasound enhances drug delivery from these nanoparticles through a pressure-driven, contact-mediated mechanism. The results of this most recent study suggest that using local acoustic pressure to enhance drug delivery is not likely to trigger safety issues that could complicate future clinical development of this technology.
This work is detailed in a paper tiled, “Acoustic activation of targeted liquid perfluorocarbon nanoparticles does not compromise endothelial cell integrity.” An abstract of this paper is available at the journal’s website.