Quantification of Optison bubble size and lifetime during sonication dominant role of secondary cavitation bubbles causing acoustic bioeffects
Quantification of Optison bubble size and lifetime during sonication dominant role of secondary cavitation bubbles causing acoustic bioeffects
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DOI：
10.1121/1.1624073
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发表时间：
2004-04-01
影响因子：
2.4
通讯作者：
Prausnitz, MR
中科院分区：
文献类型：
--
作者：
Kamaev, PP;Hutcheson, JD;Prausnitz, MR
声空化已被证明可以将分子输送到活细胞中，这在药物和基因输送应用中具有重要意义。为了解决这些声学生物效应的机制，这项工作测量了白蛋白稳定的空化气泡(Optison)的寿命，并将其与理想的(细胞内分子摄取)和不良的(细胞活力丧失)生物效应相关联。Optison暴露在500 kHz的超声波下(声压0.6-3.0兆帕，能量暴露0.2-200J/cm(2))，无论是否有DU145前列腺癌细胞(10(6)个/毫升)沐浴在钙黄绿素中，钙黄绿素是一种对细胞无效的示踪分子。用库尔特计数器和流式细胞仪测定泡泡寿命，用流式细胞仪评价生物效应。随着声能暴露的增加，Optison空化核的寿命缩短，生物效应(分子摄取和细胞活力损失)增加。这些生物效应与气泡的消失有很好的相关性，表明造影剂破坏直接或间接影响细胞，可能涉及Optison破坏时产生的不稳定的空化核。由于Optison溶液预先破坏了所有可检测到的气泡，也造成了显著的生物效应，因此更有可能是涉及次生空化气泡的间接机制。(C)2004年美国声学学会。
Acoustic cavitation has been shown to deliver molecules into viable cells, which is of interest for drug and gene delivery applications. To address mechanisms of these acoustic bioeffects, this work measured the lifetime of albumin-stabilized cavitation bubbles (Optison) and correlated it with desirable (intracellular uptake of molecules) and undesirable (loss of cell viability) bioeffects. Optison was exposed to 500 kHz ultrasound (acoustic pressures of 0.6-3.0 MPa and energy exposures of 0.2-200 J/cm(2)) either with or without the presence of DU145 prostate cancer cells (10(6) cells/ml) bathed in calcein, a cell-impermeant tracer molecule. Bubble lifetime was determined using a Coulter counter and flow cytometer, while bioeffects were evaluated by flow cytometry. The lifetime of Optison cavitation nuclei was found to decrease and bioeffects (molecular uptake and loss of cell viability) were found to increase with increasing acoustic energy exposure. These bioeffects correlated well with the disappearance of bubbles, suggesting that contrast agent destruction either directly or indirectly affected cells, probably involving unstabilized cavitation nuclei created upon the destruction of Optison. Because Optison solutions presonicated to destroy all detectable bubbles also caused significant bioeffects, the indirect mechanism involving secondary cavitation bubbles is more likely. (C) 2004 Acoustical Society of America.