Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia.
Radiol Oncol. 2010 Mar;44(1):34-41. doi: 10.2478/v10019-010-0002-3. Epub 2010 Mar 18.
In order to reduce the side-effects of chemotherapy, combined chemotherapy-electroporation (electrochemotherapy) has been suggested. Electroporation, application of appropriate electric pulses to biological cells, can significantly enhance molecular uptake of cells due to formation of transient pores in the cell membrane. It was experimentally demonstrated that the efficiency of electroporation is under the control of electric pulse parameters. However, the theoretical basis for these experimental results is not fully explained. In order to predict the outcome of experiments and optimize the efficiency of electroporation before each treatment, we developed a model to investigate the effect of pulse shape on efficiency of electroporation.
Our model is based on a developed chemical-kinetics scheme and trapezium barrier model, while self-consistency was taken into account. This model is further supplemented with a molecular transport model to acquire the molecular uptake of cells. The investigated pulse shapes in this study were unipolar rectangular pulses with different rise and fall times, triangular, sinusoidal and bipolar rectangular pulses and also sinusoidal modulated unipolar pulses with different percentages of modulation. The obtained results from our modelling and simulations are in good agreement with previously published experimental results.
We therefore conclude that this model can be used to predict the effects of arbitrarily shaped electroporation pulses on cell membrane conductivity and molecular transport across the cell membrane.
为了降低化疗的副作用，联合化疗-电穿孔（电化疗）已被提出。电穿孔，即向生物细胞施加适当的电脉冲，可以由于细胞膜中形成瞬时孔而显著增强细胞的分子摄取。实验证明，电穿孔的效率受电脉冲参数的控制。然而，这些实验结果的理论基础并没有得到充分解释。为了预测实验结果并在每次治疗前优化电穿孔的效率，我们开发了一个模型来研究脉冲形状对电穿孔效率的影响。
我们的模型基于一个开发的化学动力学方案和梯形势垒模型，同时考虑了自洽性。该模型进一步补充了分子输运模型以获得细胞的分子摄取。本研究中研究的脉冲形状是具有不同上升和下降时间的单极矩形脉冲、三角脉冲、正弦脉冲和双极矩形脉冲，以及具有不同调制百分比的正弦调制单极脉冲。我们从建模和模拟中获得的结果与之前发表的实验结果非常吻合。
因此，我们得出结论，该模型可用于预测任意形状的电穿孔脉冲对细胞膜电导率和跨细胞膜分子输运的影响。
