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The importance of electric field distribution for effective in vivo electroporation of tissues.

机译:电场分布对于有效体内组织电穿孔的重要性。

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摘要

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.
机译:暴露于短而强的电脉冲的细胞可渗透多种离子分子。这种现象被称为电穿孔或电透化,被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关注。但是,电极的几何形状和分布尚未得到充分解决。到目前为止,大多数电极都是凭经验确定的。在我们的研究中,我们:1)设计了两个电极组,它们在肿瘤中产生明显不同的电场分布; 2)通过磁共振电流密度成像对两个电极组的电流密度分布进行定性评估; 3)使用三维有限元模型以计算两个电极组的电场值,并且4)证明了这两个电极组在小鼠肿瘤模型中的电化学疗法有效性不同。我们的研究结果清楚地表明,数值模型是可靠的,并且在进一步寻找使电化学疗法和体内电穿孔通常更有效的电极方面非常有用。我们的研究还表明,用足够高的电场更好地覆盖肿瘤对于提高电化学疗法的有效性是必要的。

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