The Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, PR China.
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, PR China; UMR Inserm U930, Université François-Rabelais de Tours, Tours, France.
Ultrason Sonochem. 2018 Oct;47:141-150. doi: 10.1016/j.ultsonch.2018.02.004. Epub 2018 Feb 6.
In this study, the bioeffects of acoustic droplet vaporization (ADV) on adjacent cells were investigated by evaluating the real-time cell response at the single-cell level in situ, using a combined ultrasound-exposure and optical imaging system. Two imaging modalities, high-speed and fluorescence imaging, were used to observe ADV bubble dynamics and to evaluate the impact on cell membrane permeabilization (i.e., sonoporation) using propidium iodide (PI) uptake as an indicator. The results indicated that ADV mainly led to irreversible rather than reversible sonoporation. Further, the rate of irreversible sonoporation significantly increased with increasing nanodroplet concentration, ultrasound amplitude, and pulse duration. The results suggested that sonoporation is correlated to the rapid formation, expansion, and contraction of ADV bubbles near cells, and strongly depends on ADV bubble size and bubble-to-cell distance when subjected to short ultrasound pulses (1 μs). Moreover, the displacement of ADV bubbles was larger when using a long ultrasound pulse (20 μs), resulting in considerable cell membrane deformation and a more irreversible sonoporation rate. During sonoporation, cell membrane blebbing as a recovery manoeuvre was also investigated, indicating the essential role of Ca influx in the membrane blebbing response. This study has helped us gain further insights into the dynamic behavior of ADV bubbles near cells, ADV bubble-cell interactions, and real-time cell response, which are invaluable in the development of optimal approaches for ADV-associated theranostic applications.
在这项研究中，通过使用联合超声暴露和光学成像系统，在原位评估单细胞水平的实时细胞反应，研究了声致液滴汽化（ADV）对相邻细胞的生物效应。使用两种成像方式，高速和荧光成像，观察 ADV 气泡动力学，并使用碘化丙啶（PI）摄取作为指示剂评估对细胞膜通透性（即声孔）的影响。结果表明，ADV 主要导致不可逆而非可逆的声孔。此外，不可逆声孔的速率随着纳米液滴浓度、超声幅度和脉冲持续时间的增加而显著增加。结果表明，声孔与细胞附近 ADV 气泡的快速形成、膨胀和收缩有关，并且当短超声脉冲（1 μs）作用时强烈依赖于 ADV 气泡的大小和气泡与细胞的距离。此外，当使用长超声脉冲（20 μs）时，ADV 气泡的位移更大，导致相当大的细胞膜变形和不可逆声孔的更高速率。在声孔期间，还研究了细胞膜起泡作为一种恢复机制，表明 Ca 流入在膜起泡反应中的重要作用。这项研究帮助我们进一步了解了细胞附近 ADV 气泡的动态行为、ADV 气泡-细胞相互作用以及实时细胞反应，这对于开发与 ADV 相关的治疗应用的最佳方法非常有价值。
