Biophysical Research Group, Faculty of Natural Sciences, Vytautas Magnus University, Vileikos g. 8, Kaunas, Lithuania.
Sci Rep. 2020 May 8;10(1):7743. doi: 10.1038/s41598-020-64213-y.
The concurrent assessment of principal sonoporation factors has been accomplished in a single systemic study. Microbubble sonodestruction dynamics and cavitation spectral characteristics, ultrasound scattering and attenuation, were examined in relation to the intracellular delivery of anticancer drug, bleomycin. Experiments were conducted on Chinese hamster ovary cells coadministered with Sonovue microbubbles. Detailed analysis of the scattering and attenuation temporal functions culminated in quantification of metrics, inertial cavitation dose and attenuation rate, suitable for cavitation control. The exponents, representing microbubble sonodestruction kinetics were exploited to derive dosimetric, microbubble sonodestruction rate. High intracorrelation between empirically-attained metrics defines the relations which indicate deep physical interdependencies within inherent phenomena. Subsequently each quantified metric was validated to be well-applicable to prognosticate the efficacy of bleomycin delivery and cell viability, as indicated by strong overall correlation (R > 0.85). Presented results draw valuable insights in sonoporation dosimetry and contribute towards the development of universal sonoporation dosimetry model. Both bleomycin delivery and cell viability reach their respective plateau levels by the time, required to attain total microbubble sonodestruction, which accord with scattering and attenuation decrease to background levels. This suggests a well-defined criterion, feasible through signal-registration, universally employable to set optimal duration of exposure for efficient sonoporation outcome.
在一项系统研究中，同时评估了主要声孔形成因素。研究了微泡超声破坏动力学和空化光谱特性、超声散射和衰减与抗癌药物博来霉素细胞内递呈的关系。在与 SonoVue 微泡共同给药的中国仓鼠卵巢细胞上进行了实验。散射和衰减时间函数的详细分析最终量化了适用于空化控制的指标，惯性空化剂量和衰减率。代表微泡超声破坏动力学的指数被用来推导出剂量学、微泡超声破坏率。经验获得的度量之间的高相关性定义了关系，表明固有现象之间存在深刻的物理相互依存关系。随后，每个量化的指标都经过验证，可很好地预测博来霉素递呈和细胞活力的效果，这表明具有很强的整体相关性（R>0.85）。所呈现的结果为声孔形成剂量学提供了有价值的见解，并为开发通用声孔形成剂量学模型做出了贡献。博来霉素的递呈和细胞活力都在达到总微泡超声破坏所需的时间内达到各自的平台水平，这与散射和衰减降低到背景水平一致。这表明通过信号登记，可以实现一个明确的标准，普遍适用于为高效声孔形成效果设置最佳暴露时间。
