Centro Atómico Constituyentes, Comisión Nacional de Energía Atómica, Buenos Aires, Argentina.
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad de Buenos Aires, Instituto de Fısica del Plasma (INFIP), Buenos Aires, Argentina.
Bioelectrochemistry. 2021 Aug;140:107788. doi: 10.1016/j.bioelechem.2021.107788. Epub 2021 Feb 24.
The use of electrochemotherapy (ECT) is a well-established technique to increase the cellular uptake of cytotoxic agents within certain cancer treatment strategies. The study of the mechanisms that take part in this complex process is of high interest to gain a deeper knowledge of it, enabling the improvement of these strategies. In this work, we present a coupled multi-physics electroporation model based on a related previous one, to describe the effect of a set of electric pulses on cisplatin transport across the plasma membrane. The model applies a system of partial differential equations that includes Poisson's equation for the electric field, Nernst-Planck's equation for species transport, Maxwell's tensor and mechanical equilibrium equation for membrane deformation and Smoluchowski's equation for pore creation dynamics. Our numerical results were compared with previous numerical and experimental published data with good qualitative and quantitative agreement. These results indicate that pore aperture is favored at the cell poles by the electric field and mechanical stress forces, giving support to the dominant hypothesis of hydrophilic pore creation as the main mechanism of drug entry during an ECT treatment.
电化学疗法 (ECT) 的应用是一种成熟的技术，可增加某些癌症治疗策略中细胞对细胞毒性药物的摄取。研究参与这一复杂过程的机制对于深入了解这一过程非常重要，从而能够改进这些策略。在这项工作中，我们提出了一个基于相关前期工作的耦合多物理电穿孔模型，以描述一组电脉冲对顺铂跨质膜转运的影响。该模型应用了一组偏微分方程，包括电场的泊松方程、物种传输的能斯特-普朗克方程、膜变形的麦克斯韦张量和力学平衡方程以及孔创建动力学的斯莫鲁霍夫斯基方程。我们的数值结果与之前发表的数值和实验数据进行了比较，具有良好的定性和定量一致性。这些结果表明，电场和机械应力力有利于在细胞极处形成孔，支持亲水孔创建作为 ECT 治疗过程中药物进入的主要机制的主要假设。
