Journal
ULTRASOUND IN MEDICINE AND BIOLOGY
Volume 31, Issue 12, Pages 1693-1700Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ultrasmedbio.2005.07.022
Keywords
ultrasound; acoustic radiation forces; contrast agent; nanoparticle; targeted drug delivery; lipid exchange; membrane fusion
Funding
- NCI NIH HHS [CO-37007] Funding Source: Medline
- NHLBI NIH HHS [HL-42950] Funding Source: Medline
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Liquid perfluorocarbon nanoparticles serve as sensitive and specific targeted contrast and drug delivery vehicles by binding to specific cell surface markers. We hypothesized that application of acoustic energy at diagnostic power levels could promote nanoparticle-associated drug delivery by stimulating increased interaction between the nanoparticle's lipid layer and the targeted cell's plasma membrane. Ultrasound (mechanical index = 1.9) applied with a conventional ultrasound imaging system to nanoparticles targeted to alpha(v)beta(3)-integrins on C32 melanoma cancer cells in vitro produced no untoward effects. Within 5 min, lipid delivery from nanoparticles into cell cytoplasm was dramatically augmented. We also demonstrate the operation of a potential physical mechanism for this effect, the acoustic radiation force on the nanoparticles, which may contribute to the enhanced lipid delivery. Accordingly, we propose that local delivery of lipophilic substances (e.g., drugs) from targeted nanoparticles directly into cell cytoplasm can be augmented rapidly and safely with conventional ultrasound imaging devices through nondestructive mechanisms. (E-mail: saw@wuphys.wustl.edu) (c) 2005 World Federation for Ultrasound in Medicine & Biology.
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