Application of ultrasound to selectively localize nanodroplets for targeted imaging and therapy
Application of ultrasound to selectively localize nanodroplets for targeted imaging and therapy
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DOI：
10.2310/7290.2006.00019
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发表时间：
2006-07-01
影响因子：
2.8
通讯作者：
Ferrara, Katherine W.
中科院分区：
文献类型：
--
作者：
Dayton, Paul A.;Zhao, Shukui;Ferrara, Katherine W.
脂质包裹的全氟碳纳米液滴是一种直径亚微米、充满液体的液滴，在分子靶向治疗和超声成像中具有潜在的应用前景。超声分子成像的独特之处在于，这些试剂的最佳应用不仅取决于表面化学，还取决于所应用的超声场，它可以增加受体与配体的结合和膜的融合。理论和实验相结合证明了全氟碳纳米颗粒在超声传播方向上的位移，其中，峰值压力在兆帕数量级、频率在兆赫范围内的行进超声波产生的粒子平移速度与声强成正比，并随着中心频率的增加而增加。在直径为数百微米或更大的容器内，会产生每秒数百微米的颗粒速度，液滴置换的主要机制被证明是大体积流体流动。建立了粒子的辐射力置换模型，并论证了粒子的有效置换在微血管系统中是可行的。在流动系统中，目标液滴的声学操作增加了液滴的滞留。此外，我们还论证了超声增强的粒子内化和治疗输送的可行性。
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.