Journal
MOLECULAR IMAGING
Volume 5, Issue 3, Pages 160-174Publisher
SAGE PUBLICATIONS INC
DOI: 10.2310/7290.2006.00019
Keywords
targeted imaging; targeted drug delivery; ultrasound; nanoparticles; nanodroplets; radiation force; acoustic streaming
Funding
- NCI NIH HHS [N01 CO 37118, R01 CA 103828, R01 CA103828] Funding Source: Medline
- NIAID NIH HHS [N01CO37118] Funding Source: Medline
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Lipid-coated perfluorocarbon nanodroplets are submicrometer-diameter liquid-filled droplets with proposed applications in molecularly targeted therapeutics and ultrasound (US) imaging. Ultrasonic molecular imaging is unique in that the optimal application of these agents depends not only on the surface chemistry, but also on the applied US field, which can increase receptor-ligand binding and membrane fusion. Theory and experiments are combined to demonstrate the displacement of perfluorocarbon nanoparticles in the direction of US propagation, where a traveling US wave with a peak pressure on the order of megapascals and frequency in the megahertz range produces a particle translational velocity that is proportional to acoustic intensity and increases with increasing center frequency. Within a vessel with a diameter on the order of hundreds of micrometers or larger, particle velocity on the order of hundreds of micrometers per second is produced and the dominant mechanism for droplet displacement is shown to be bulk fluid streaming. A model for radiation force displacement of particles is developed and demonstrates that effective particle displacement should be feasible in the microvasculature. In a flowing system, acoustic manipulation of targeted droplets increases droplet retention. Additionally, we demonstrate the feasibility of US-enhanced particle internalization and therapeutic delivery.
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