Effect of non-acoustic parameters on heterogeneous sonoporation mediated by single-pulse ultrasound and microbubbles
Effect of non-acoustic parameters on heterogeneous sonoporation mediated by single-pulse ultrasound and microbubbles
复制标题
非声学参数对单脉冲超声和微泡介导的异质声孔作用的影响
DOI：
10.1016/j.ultsonch.2015.12.001
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发表时间：
2016-07-01
影响因子：
8.4
通讯作者：
Yu, Alfred C. H.
中科院分区：
文献类型：
--
作者：
Qin, Peng;Xu, Lin;Yu, Alfred C. H.
声穿孔是超声波与微泡相互作用引起的短暂质膜穿孔，在药物输送和基因治疗中显示出巨大的潜力。然而，声致穿孔的异质性在实现可控和可预测的药物递送方面引入了复杂性和挑战。本研究的目的是了解非声学参数（气泡相关和气泡-细胞相互作用参数）如何影响声致孔作用。使用定制的超声曝光和荧光成像平台，我们观察了单细胞水平的声致孔动力学，并定量外源分子摄取水平以表征声致孔的程度。引入Sonovue微泡以被动调节微泡到细胞的距离和数量以及气泡大小。施加具有10个周期脉冲持续时间的1 MHz超声和0.6MPa峰值负压以触发微泡的惯性塌陷。我们的数据揭示了非声学参数对声孔作用的异质性的影响。(i)相对小的气泡（直径，D < 5.5 μ m）的局部塌陷导致可预测的声致穿孔，其程度取决于气泡到细胞的距离（d）。当d/D > 1时，没有观察到声致穿孔，而当d/D < 1时，发生可逆的声致穿孔。(ii)大气泡（D > 5.5 μ m）在大距离上表现出平移运动，导致不可预测的声致穿孔。朝向细胞表面的翻译导致可变的可逆声致穿孔或不可逆声致穿孔，而远离细胞的翻译导致无声致穿孔或可逆声致穿孔。(iii)当D < 5.5 μ m和d/D < 1时，气泡数与声孔程度呈正相关。两到三个气泡的局部破裂主要导致可逆声孔作用，而不可逆声孔作用更可能在四个或更多气泡破裂后发生。这些研究结果提供了有用的洞察非声学参数和声致穿孔的程度之间的关系。(C)2015 Elsevier B. V.版权所有。
Sonoporation-transient plasma membrane perforation elicited by the interaction of ultrasound waves with microbubbles-has shown great potential for drug delivery and gene therapy. However, the heterogeneity of sonoporation introduces complexities and challenges in the realization of controllable and predictable drug delivery. The aim of this investigation was to understand how non-acoustic parameters (bubble related and bubble-cell interaction parameters) affect sonoporation. Using a customized ultrasound-exposure and fluorescence-imaging platform, we observed sonoporation dynamics at the single-cell level and quantified exogenous molecular uptake levels to characterize the degree of sonoporation. Sonovue microbubbles were introduced to passively regulate microbubble-to-cell distance and number, and bubble size. 1 MHz ultrasound with 10-cycle pulse duration and 0.6 MPa peak negative pressure were applied to trigger the inertial collapse of microbubbles. Our data revealed the impact of non-acoustic parameters on the heterogeneity of sonoporation. (i) The localized collapse of relatively small bubbles (diameter, D < 5.5 mu m) led to predictable sonoporation, the degree of which depended on the bubble-to-cell distance (d). No sonoporation was observed when d/D > 1, whereas reversible sonoporation occurred when d/D < 1. (ii) Large bubbles (D > 5.5 mu m) exhibited translational movement over large distances, resulting in unpredictable sonoporation. Translation towards the cell surface led to variable reversible sonoporation or irreversible sonoporation, and translation away from the cell caused either no or reversible sonoporation. (iii) The number of bubbles correlated positively with the degree of sonoporation when D < 5.5 mu m and d/D < 1. Localized collapse of two to three bubbles mainly resulted in reversible sonoporation, whereas irreversible sonoporation was more likely following the collapse of four or more bubbles. These findings offer useful insight into the relationship between non-acoustic parameters and the degree of sonoporation. (C) 2015 Elsevier B.V. All rights reserved.