Control of Acoustic Cavitation for Efficient Sonoporation with Phase-Shift Nanoemulsions.
Control of Acoustic Cavitation for Efficient Sonoporation with Phase-Shift Nanoemulsions.
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DOI：
10.1016/j.ultrasmedbio.2018.12.001
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发表时间：
2019-03
影响因子：
2.9
通讯作者：
Porter TM
中科院分区：
文献类型：
--
作者：
Burgess MT;Porter TM
声空化可用于暂时破坏细胞膜以用于大生物分子的细胞内递送。术语声致穿孔，这种技术用于有效细胞内递送的能力（即，>50%的初始细胞群体显示摄取）同时维持细胞活力（即，>50%的初始细胞群体存活）已被证明是非常困难的。在这里，我们报告，相移纳米乳液（PSNES）的功能作为惯性空化核，提高声孔效率。实验研究了超声频率、微泡动力学和声孔效率之间的相互作用。在1，2.5和5 MHz的短脉冲超声声液滴蒸发期间和之后，使用宽带被动空化检测器捕获从PSNES成核的单个微泡的声发射。分析了被动空化探测器信号的时域特征，利用瑞利坍塌模型估计了微气泡的最大尺寸（Rmax）。然后将这些结果应用于声致穿孔实验，以测试吸收效率是否取决于惯性塌陷前的最大微泡尺寸。结果表明，在1、2.5和5 MHz下，在声学液滴蒸发阈值下，Rmax分别约为61.7 ± 5.2、24.9 ± 2.8和12.4 ± 2.1 μm。声穿孔效率在较高频率下增加，在1、2.5和5MHz下的效率分别为39.5 ± 13.7%、46.6 ± 3.28%和66.8 ± 5.5%。由于高能惯性空化的侵蚀作用，在较低频率下观察到过度的细胞损伤。这些结果突出了声空化控制在确定声孔实验结果中的重要性。此外，PSNE可以用作其他治疗超声应用的可定制惯性空化核。
Acoustic cavitation can be used to temporarily disrupt cell membranes for intracellular delivery of large biomolecules. Termed sonoporation, the ability of this technique for efficient intracellular delivery (i.e., >50% of initial cell population showing uptake) while maintaining cell viability (i.e., >50% of initial cell population viable) has proven to be very difficult. Here, we report that phase-shift nanoemulsions (PSNEs) function as inertial cavitation nuclei for improvement of sonoporation efficiency. The interplay between ultrasound frequency, resultant microbubble dynamics and sonoporation efficiency was investigated experimentally. Acoustic emissions from individual microbubbles nucleated from PSNEs were captured using a broadband passive cavitation detector during and after acoustic droplet vaporization with short pulses of ultrasound at 1, 2.5 and 5 MHz. Time domain features of the passive cavitation detector signals were analyzed to estimate the maximum size (Rmax) of the microbubbles using the Rayleigh collapse model. These results were then applied to sonoporation experiments to test if uptake efficiency is dependent on maximum microbubble size before inertial collapse. Results indicated that at the acoustic droplet vaporization threshold, Rmax was approximately 61.7 ± 5.2, 24.9 ± 2.8, and 12.4 ± 2.1 μm at 1, 2.5 and 5 MHz, respectively. Sonoporation efficiency increased at higher frequencies, with efficiencies of 39.5 ± 13.7%, 46.6 ± 3.28% and 66.8 ± 5.5% at 1, 2.5 and 5 MHz, respectively. Excessive cellular damage was seen at lower frequencies because of the erosive effects of highly energetic inertial cavitation. These results highlight the importance of acoustic cavitation control in determining the outcome of sonoporation experiments. In addition, PSNEs may serve as tailorable inertial cavitation nuclei for other therapeutic ultrasound applications.
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