Analysis of Metrics for Molecular Sonotransfer in Vitro
Analysis of Metrics for Molecular Sonotransfer in Vitro
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DOI：
10.1021/acs.molpharmaceut.5b00347
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发表时间：
2015-10-01
影响因子：
4.9
通讯作者：
Satkauskas, Saulius
中科院分区：
文献类型：
--
作者：
Maciulevicius, Martynas;Tamosiunas, Mindaugas;Satkauskas, Saulius
超声诱导的微泡(MB)空化被用来显著增强细胞膜的通透性，从而允许将各种治疗剂输送到细胞中。为了监测和定量控制空化程度，需要建立统一的剂量学模型。在本研究中，我们同时对三个主要的声学效应因素进行了定量评估：(1)MB浓度，(2)MB空化程度，(3)阿霉素(DOX)声导入中国仓鼠卵巢细胞。MB浓度测量结果和被动记录的MB空化信号分别用于MB声破坏率和频谱均方根(EMS)计算。随后，对每个声压值进行RMS达到最大值的时间和惯性空化剂量(ICD)定量。这一综合研究不仅解释了ICD和MB声破坏率的关系，而且开发了一种新的声学测量指标：EMS时间与最大值的倒数(1/EMS最大值的时间)。ICD和MB的声破坏率与DOX声传输的相关性和相关性表明，惯性空化是细胞声穿孔的关键机制。所有这些指标都被成功地用于阿霉素的超声转移预测(R-2>；0.9，p<；0.01)，因此表明了将其应用于未来超声介导的药物和基因传递的剂量学应用的可行性。
Ultrasound induced microbubble (MB) cavitation is used to significantly enhance cell membrane permeabilization, thereby allowing delivery of various therapeutic agents into cells. In order to monitor and quantitatively control the extent of cavitation the uniform dosimetry model is needed. In present study we have simultaneously performed quantitative evaluation of three main sonoporation factors: (1) MB concentration, (2) MB cavitation extent, and (3) doxorubicin (DOX) sonotransfer into Chinese hamster ovary cells. MB concentration measurement results and passively recorded MB cavitation signals were used for MB sonodestruction rate and spectral root-mean-square (EMS) calculations, respectively. Subsequently, time to maximum value of RMS and inertial cavitation dose (ICD) quantifications were performed for every acoustic pressure value. This comprehensive research has led not only to explanation of relation of ICD and MB sonodestruction rate but also to the development of a new sonoporation metric: the inverse of time to maximum value of EMS (1/time to maximum value of EMS). ICD and MB sonodestruction rate intercorrelation and correlation with DOX sonotransfer suggest inertial cavitation to be the key mechanism for cell sonoporation. All these metrics were successfully used for doxorubicin sonotransfer prediction (R-2 > 0.9, p < 0.01) and therefore shows feasibility to be applied for future dosimetric applications for ultrasound-mediated drug and gene delivery.