Ultrashort Pulsed electric fields modulation of ION channels as a novEl thERapeutic approach – PIONEER

High-intensity nanosecond pulsed electric field (nsPEF) stimulation stands out as an exceptional technique for membrane and intracellular manipulation. Over the past two decades, extensive research has explored the unique capability of pulses lasting hundreds of ns to initiate programmed cell death and trigger immune responses, leading to the first successful clinical trial for treating cancer. Compared to other approaches, nsPEF stimulation offers localized tumor ablation, minimizing harm to healthy tissues surrounding the tumor, eliminating the need for chemotherapy, and reducing side effects. Nonetheless, the primary limitation that still exists is the requirement to surgically implant electrodes into the skin for pulse delivery, a hurdle that can be potentially overcome using cutting-edge propagative antennas capable of remotely delivering pulses. Indeed, shortening pulses to durations < 100 ns offers the possibility of using contactless technologies for PEF delivery. Therefore, due to remarkable advancements in pulsed power technologies, bioelectric investigations have recently shifted towards ultrashort pulses (usPEF) including nsPEF with durations lower or equal to 10 ns or even pulses as brief as hundreds of picoseconds (psPEF) that are highly attractive for the further development of a wide range of minimally invasive and drug-free therapies, beyond cancer, including, cardiac defibrillation or neurostimulation. PIONEER aims to push forward the exploration of the potential of usPEF-induced bioeffects for a groundbreaking therapeutic approach that centers on the interplay between short electric pulses and ion channels, i.e., pore-forming membrane proteins that control ion traffic across membranes.