Augmented and selective delivery of liquid perfluorocarbon nanoparticles to melanoma cells with noncavitational ultrasound

Our laboratory previously has demonstrated the ability of liquid perfluoro-carbon (PFC) nanoparticles to serve as site-targeted contrast and therapeutic agents by specifically binding molecular markers. In this study, we sought to enhance the delivery of targeted PFC nanoparticles to cells expressing the integrin α_vβ₃ using clinical levels of ultrasound energy. Using an Acuson Sequoia imager, we demonstrate that ultrasound applied at 2MHz and 1.9 mechanical index (MI) for a five minute duration enhances the cellular interaction of targeted perfluorocarbon nanoparticles by melanoma cancer cells in vitro without any untoward effect from the ultrasound energy itself upon either the cells or the perfluorocarbon nanoparticles. Employing a custom designed specimen chamber, we have visualized a fundamental physical mechanism for this effect, that of acoustic radiation force (primary and secondary) on the particles, that may contribute to enhanced delivery. Accordingly, our study shows that enhancement of cellular interaction with targeted nanoparticles is feasible by noncavitational mechanisms. Ultrasonically-enhanced delivery of tracers or drugs to a wide variety of pathologic tissues may be useful for augmenting drug delivery after targeting, while limiting untoward effects on other tissues.