Nanoelectroablation for human carcinoma therapy

Abstract

We have developed a low energy direct current pulsed electric field therapy for tissue ablation. This therapy applies 100 ns long electric pulses 30 kV/cm in amplitude using a contact electrode and triggers apoptosis in the treated tissue. Here we review the progress that has been made in understanding the mechanisms and targets of nanosecond pulsed electric fields (nsPEF) when applied to cells and tissues. This work began in 2001 in the laboratory of Karl Schoenbach who collaborated with biologists Stephen Beebe and Stephen Buescher to demonstrate the permeabilization of intracellular organelles. Since then over 100 papers have been published studying the cellular responses to nsPEF. We discuss these targets and cellular responses and introduce some new results from our group using nanoelectroablation to treat human pancreatic carcinoma in a murine xenograft model system. We have determined that 500 pulses 100 ns long and 30 kV/cm in amplitude are sufficient to ablate human pancreatic carcinomas growing in immunosuppressed mice and these ablated tumors do not recur for at least 300 days. We have also determined that the reactive oxygen species generation that is triggered within a minute after nsPEF treatment is Ca 2+ -dependent. In order bring this therapy into the clinic for the treatment of human tumors we are developing both a pulse generator as well as delivery electrodes to target the tumors to be treated. We describe the NanoBlate ® Model NB-1 100 ns pulse generator and the first human clinical trial data using nanoelectroablation to ablate basal cell carcinomas without scarring.

Conductive Cellulose Bio‐Nanosheets Assembled Biostable Hydrogel for Reliable Bioelectronics

“…Previous studies have demonstrated that a high electrical voltage intensity can induce cell apoptosis or death by causing electroporation of the cell membrane, thereby increasing the amount of intracellular Ca 2+ and reactive oxygen species that are toxic to cells. [48][49][50][51][52] In summary, upon adequate electrical stimulation (≈300 mV), the PGCNSH strengthens the effect of electrical signals because the interconnected conductive network formed by the PGC bio-nanosheets inside the PGCNSH provides short circuit for the electrical current to pass through neighboring electrodes, and thereby spatiotemporally imparting biochemical and biophysical cues to manipulate cell behavior. Consequently, the electrical stimulation and PGCNSH synergistically enhance the myoblast maturation.…”