Impact of the Use of Nanoparticles on Electric Field Distribution during Irreversible Electroporation Treatments: Can the Lesion be Enhanced Beyond IRE Margin?

Abstract

Irreversible electroporation (IRE) is the phenomenon in which cell transmembrane potential is increased by exposure to short, high intensity electric fields. When a certain threshold is reached, damage to the cell and homeostasis disruption is too great for recovery and cell death occurs. IRE has gained a lot of attention as a cancer ablation technique to treat otherwise inoperable tumors due to its non-thermal mechanism to induce cell death. This characteristic makes it particularly attractive to treat pancreatic tumors since it is often claimed that in contrast with thermal ablation techniques, irreversible electroporation decreases damage to large blood vessels, such as the superior mesenteric artery, and neighboring bile ducts. Furthermore, recent studies on the use of nanoparticles with IRE show great potential for an increased selectivity to ablate cancer cells while sparing a higher percentage of healthy tissue. The goal of the study presented here is to numerically analyze the relevance of such increase in treated volume in a 3D in vitro tumor model and how it compares to experimental results and its translation to the clinical setting. A 3D tumor model was implemented for numerical simulations to make predictions of lesion enhancement after IRE treatment with nanoparticles (NPs). Results were compared to those obtained through in vitro experiments in 3D hydrogel tumor constructs. These comparisons indicate that a lesion volume increase can be obtained through enhanced sensitization of cancer cells beyond IRE margin. This can be clinically significant for the use of IRE to treat tumors with intricate morphologies such as those with infiltrative fingering margins, and those near or engulfing critical structures.