Electrochemotherapy Using Doxorubicin and Nanosecond Electric Field Pulses: A Pilot in Vivo Study.

Vitalij Novickij,Augustinas Želvys,Jurij Novickij,Austėja Balevičiūtė,Auksė Zinkevičienė,Veronika Malyško,Irutė Girkontaitė

doi:10.3390/molecules25204601

Abstract

Pulsed electric field (PEF) is frequently used for intertumoral drug delivery resulting in a well-known anticancer treatment—electrochemotherapy. However, electrochemotherapy is associated with microsecond range of electrical pulses, while nanosecond range electrochemotherapy is almost non-existent. In this work, we analyzed the feasibility of nanosecond range pulse bursts for successful doxorubicin-based electrochemotherapy in vivo. The conventional microsecond (1.4 kV/cm × 100 µs × 8) procedure was compared to the nanosecond (3.5 kV/cm × 800 ns × 250) non-thermal PEF-based treatment. As a model, Sp2/0 tumors were developed. Additionally, basic current and voltage measurements were performed to detect the characteristic conductivity-dependent patterns and to serve as an indicator of successful tumor permeabilization both in the nano and microsecond pulse range. It was shown that nano-electrochemotherapy can be the logical evolution of the currently established European Standard Operating Procedures for Electrochemotherapy (ESOPE) protocols, offering better energy control and equivalent treatment efficacy.

Highlights

Electroporation is a phenomenon of reversible [1,2] or irreversible [3] permeabilization of biological cells, which is triggered by cell polarization in pulsed electric fields (PEF)
Electrochemotherapy is associated with microsecond range of electrical pulses [9,10,11,12,13], while nanosecond range electrochemotherapy is almost non-existent [14,15,16]
The results summarized results areare summarized in dynamics of Sp2/0 tumors were evaluated throughout the experiment

Summary

Introduction

Electroporation is a phenomenon of reversible [1,2] or irreversible [3] permeabilization of biological cells, which is triggered by cell polarization in pulsed electric fields (PEF). Among the most established applications of electroporation is the treatment of cancer [4]. This allows the minimization of the dosage of chemotherapeutic drugs [5,6] and/or adverse effects during the ablation of the tumor [7]. Electrochemotherapy is associated with microsecond range of electrical pulses [9,10,11,12,13], while nanosecond range electrochemotherapy is almost non-existent [14,15,16]. Nanosecond pulses are typically used for tissue ablation, or in other words, drug-free anticancer therapy [17,18]

Methods

Results

Conclusion