Optimized nanosecond pulsed electric field therapy can cause murine malignant melanomas to self‐destruct with a single treatment

Abstract

We have identified a new, nanosecond pulsed electric field (nsPEF) therapy capable of eliminating murine melanomas located in the skin with a single treatment. When these optimized parameters are used, nsPEFs initiate apoptosis without hyperthermia. We have developed new suction electrodes that are compatible with human skin and have applied them to a xenograft nude mouse melanoma model system to identify the optimal field strength, pulse frequency and pulse number for the treatment of murine melanomas. A single treatment using the optimal pulse parameters (2,000 pulses, 100 ns in duration, 30 kV/cm in amplitude at a pulse frequency of 5-7 pulses/sec) eliminated all 17 melanomas treated with those parameters in 4 mice. This was the highest pulse frequency that we could use without raising the treated skin tumor temperature above 40°C. We also demonstrate that the effects of nsPEF therapy are highly localized to only cells located between electrodes and results in very little scarring of the nsPEF-treated skin.

Microsecond and nanosecond electric pulses in cancer treatments

“…They developed different protocols and eventually obtained the destruction of all of the 17 treated nodules in 4 mice with only one sequence of 100 ns pulses [Nuccitelli et al, 2010]. In their experiments, which included more than 300 tumors on 159 mice, they observed tumor cells with nuclear pyknosis and reduced blood flow, as well as red blood cell leakage within a few minutes after treatment [Nuccitelli et al, 2006.…”

“…The tumor response appeared dependent on the amplitude and the number of pulses along with the electrode configuration. Even though apoptosis appears to be the primary mechanism inducing cell destruction because the vascularization of the tissue is disrupted, necrosis is very likely to happen [Nuccitelli et al, 2006[Nuccitelli et al, , 2010.…”

Pulse Power Ablation of Melanoma with Nanosecond Pulsed Electric Fields

“…If all of the stored energy were released within one microsecond, the power would be one megawatt, a million times greater and if release in one nanosecond the peak power would be one gigawatt, a billion times greater. Within the last ten years, applications of ultra-high pulse power have been extended to biology and medicine [Beebe et al, 2002[Beebe et al, , 2003aBeebe and Schoenbach, 2005;Schoenbach et al, 2001Schoenbach et al, , 2004Vernier et al, 2003a,b], including the treatment of melanoma Ford et al, 2010;Nuccitelli et al, 2006Nuccitelli et al, , 2009Nuccitelli et al, , 2010. In applications of pulse power ablation for treatment of melanoma, as much as 6 kV of potential energy were release in multiple 300ns bursts at 60kV/cm into murine B16f10 melanoma cells or tumors.…”

“…These studies used the first developed electrode design for in vivo applications of pulse power to tumors. Since then significant advances with a number of electrode designs have been used Garon et al, 2007;Nuccitelli et al, 2006Nuccitelli et al, , 2010. The fibrosarcoma studies followed studies showing that pulse power with nanosecond pulsed electric fields induced markers for apoptosis in Jurkat and HL-60 cells [Beebe et al, 2002].…”

“…Consequently, nsPEF ablation induces B16f10 tumor elimination by multiple mechanisms that can bypass common cancer mutations that frequently result in chemotherapeutic resistances and metastasis. The application of nsPEF ablation is safe, has no systemic side effects, is non-or minimally invasive, leaves no scars, and provides an inexpensive and effective method to the arsenal for cancer treatment strategies Nuccitelli et al, 2006Nuccitelli et al, , 2009Nuccitelli et al, , 2010 …”