Application of ultrasound to selectively localize nanodroplets for targeted imaging and therapy

被引:94
作者
Dayton, Paul A.
Zhao, Shukui
Bloch, Susannah H.
Schumann, Pat
Penrose, Kim
Matsunaga, Terry O.
Zutshi, Reena
Doinikov, Alexander
Ferrara, Katherine W.
机构
[1] Univ Calif Davis, Davis, CA 95616 USA
[2] ImaRx Therapeut, Tucson, AZ USA
[3] Belarusian State Univ, Minsk, BELARUS
来源
MOLECULAR IMAGING | 2006年 / 5卷 / 03期
关键词
targeted imaging; targeted drug delivery; ultrasound; nanoparticles; nanodroplets; radiation force; acoustic streaming;
D O I
10.2310/7290.2006.00019
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:160 / 174
页数:15
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