The importance of electric field distribution for effective in vivo electroporation of tissues
The importance of electric field distribution for effective in vivo electroporation of tissues
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DOI：
10.1016/s0006-3495(98)77924-x
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发表时间：
1998-05-01
影响因子：
3.4
通讯作者：
Sersa, G
中科院分区：
文献类型：
--
作者：
Miklavcic, D;Beravs, K;Sersa, G
暴露于短而强的电脉冲的细胞变得可渗透许多不同的离子分子。这种现象被称为电穿孔或电透化，并广泛用于体外药物递送到细胞和基因转染。组织也可以被透化。这些基于电穿孔的新方法用于癌症治疗，即，电化学疗法和体内基因转染。因此，体内电穿孔获得了更广泛的兴趣。然而，电极几何形状和分布尚未得到充分解决。迄今为止使用的大多数电极都是凭经验确定的。在我们的研究中，我们1）设计了两种在肿瘤中产生明显不同的电场分布的电极组，2）通过磁共振电流密度成像定性评估两种电极组的电流密度分布，3）使用三维有限元模型计算两种电极组的电场值，以及4）证明了两种电极组之间在小鼠肿瘤模型中的电化学治疗有效性的差异。我们的研究结果清楚地表明，数值模型是可靠的，可以是非常有用的，在额外的搜索电极，使电化学疗法和体内电穿孔一般更有效。我们的研究还表明，用足够高的电场更好地覆盖肿瘤是提高电化学治疗效果所必需的。
Cells exposed to short and intense electric pulses become permeable to a number of various ionic molecules. This phenomenon was termed electroporation or electropermeabilization and is widely used for in vitro drug delivery into the cells and gene transfection. Tissues can also be permeabilized. These new approaches based on electroporation are used for cancer treatment, i.e., electrochemotherapy, and in vivo gene transfection. In vivo electroporation is thus gaining even wider interest. However, electrode geometry and distribution were not yet adequately addressed. Most of the electrodes used so far were determined empirically. In our study we 1) designed two electrode sets that produce notably different distribution of electric field in tumor, 2) qualitatively evaluated current density distribution for both electrode sets by means of magnetic resonance current density imaging, 3) used three-dimensional finite element model to calculate values of electric field for both electrode sets, and 4) demonstrated the difference in electrochemotherapy effectiveness in mouse tumor model between the two electrode sets. The results of our study clearly demonstrate that numerical model is reliable and can be very useful in the additional search for electrodes that would make electrochemotherapy and in vivo electroporation in general more efficient. Our study also shows that better coverage of tumors with sufficiently high electric field is necessary for improved effectiveness of electrochemotherapy.