Frequency-dependent evaluation of the role of definity in producing sonoporation of Chinese hamster ovary cells.
Frequency-dependent evaluation of the role of definity in producing sonoporation of Chinese hamster ovary cells.
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DOI：
10.7863/jum.2011.30.1.61
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发表时间：
2011-01
期刊：
影响因子：
--
通讯作者：
O'Brien WD Jr
中科院分区：
文献类型：
--
作者：
Forbes MM;Steinberg RL;O'Brien WD Jr
Sonopation使用超声(US)和超声造影剂(UCAS)来增强细胞的通透性，从而使治疗化合物能够非侵入性地输送到特定的靶细胞。本研究的目的是阐明声学作用的生物物理机制，特别是UCA的作用以及暴露频率。将脂壳八氟丙烷UCA的惯性空化(IC)阈值与产生的声学操作水平直接进行比较，以确定UCA参与产生声学操作。中国仓鼠卵巢细胞在UCA、500,000-Da荧光素异硫氰酸酯-葡聚糖和磷酸盐缓冲盐水溶液中以单层形式暴露于脉冲US(脉冲宽度，5个周期；脉冲重复频率，10 Hz)30秒，3个频率(0.92，3.2和5.6 MHz)。稀释峰压力(Pr)在4kPa~4.1 Mpa范围内变化，每个压力下进行5~7次独立重复。实验观察表明，IC可能不是声学作用的物理机制。在低于超声心动图IC阈值的压力水平(0.92 MHz时为1.27±0.32 Mpa，3.2 MHz时为0.84±0.19 Mpa，5.6 MHz时为2.57±0.26 Mpa)，均观察到了超声修复活性。在0.92 MHz、3.2 MHz和5.6 MHz下，Pr值分别为1.4、0.25和2.3 Mpa。UCA的崩溃阈值也遵循了类似的趋势。单因素方差分析表明，3个频率之间的声调活动存在差异(P=10−8)。因此，这些结果表明，在低于IC阈值的压力水平下，声旋与UCA的线性和/或非线性振荡有关。
Sonoporation uses ultrasound (US) and ultrasound contrast agents (UCAs) to enhance cell permeabilization, thereby allowing delivery of therapeutic compounds non-invasively into specific target cells. The objective of this study was to elucidate the biophysical mechanism of sonoporation, specifically the role of UCAs as well as exposure frequency. The inertial cavitation (IC) thresholds of the lipid-shelled octafluoropropane UCA were directly compared to the levels of generated sonoporation to determine the involvement of UCAs in producing sonoporation. Chinese hamster ovary cells were exposed as a monolayer in a solution of the UCA, 500,000-Da fluorescein isothiocyanate-dextran, and phosphate-buffered saline to 30 seconds of pulsed US (pulse duration, 5 cycles; pulse repetition frequency, 10 Hz) at 3 frequencies (0.92, 3.2, and 5.6 MHz). The peak rarefactional pressure (Pr) was varied over a range from 4 kPa to 4.1 MPa, and 5 to 7 independent replicates were performed at each pressure. The experimental observations demonstrated that IC was likely not the physical mechanism for sonoporation. Sonoporation activity was observed at pressure levels below the threshold for IC of the UCA (1.27 ± 0.32 MPa at 0.92 MHz, 0.84 ± 0.19 MPa at 3.2 MHz, and 2.57 ± 0.26 MPa at 5.6 MHz) for all 3 frequencies examined. The Pr values at which the peak sonoporation activity occurred were 1.4 MPa at 0.92 MHz, 0.25 MPa at 3.2 MHz, and 2.3 MPa at 5.6 MHz. The UCA collapse thresholds followed a similar trend. A 1-way analysis of variance test confirmed that sonoporation activity differed among the 3 frequencies examined (P = 10−8). These results thus suggest that sonoporation is related to linear and/or nonlinear oscillation of the UCA occurring at pressure levels below the IC threshold.
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