Non-ionizing radiation generated by nanosecond pulsed electric fields (nsPEFS) induce apoptosis in cancer in vivo

Summary form only given. Over the last several years pulse power technology has developed into a novel and innovative time domain nanotechnology as a new modality to treat cancer. The technology treats cancer in the absence of drugs by generating non-ionizing radiation with nanosecond pulsed electric fields (nsPEFs or nanopulses) that are high in power (gigawatts) and low in energy (millijoules). They can induce apoptosis and cause loss of vascular viability contributing to infarctive tumor death in a temperature-independent manner. NsPEFs have effects distinct from conventional electroporation (EP) used in irreversible EP and electrochemotherapy with bleomycin. Nanopulses affect intracellular structures and functions while having unique, non-EP effects on plasma membranes. Unlike cancer therapies that induce necrosis through lethal cryotherapy or hyperthermia, such as radiofrequency ablation, nanopulses convey intense, high power, non-thermal electric fields to the tumor mass, sparing adjacent tissues and resulting in the elimination of tumors. NsPEFs induced apoptosis in all tumor cells tested in vitro. In addition, nsPEFs induced apoptosis in fibrosarcoma tumors and significantly reduced tumor size. Apoptosis is a form of programmed cell death that is altruistic cell suicide that eliminates cells that are senescent, damaged, diseased or not needed such that surrounding cells are spared the damage by inflammation. During apoptosis cells undergo an orchestrated disassembly of cell structure and function by proteases called caspases. The apoptotic cells are phagocytized by other cells such that the cell raw materials can be recycled. Apoptosis is the antithesis of death by necrosis, where cell membrane integrity fails and cells leak their contents into the surrounding environment leading to inflammation, pain and scarring. Indicators of apoptosis in fibrosarcoma tumors included caspase activation and DNA fragmentation (degradation). The use of nsPEFs as a non-therma- - l, non-ionizing radiation modality without chemotherapeutic agents will provide a basis for future clinical studies to treat cancers. The application of nsPEFs is safe and relatively inexpensive. Unlike chemotherapy it does not have systemic side effects and unlike surgery it is minimally invasive and leaves no scars. The therapeutic application of nsPEFs can provide an inexpensive, non-invasive, new, novel, and effective method to the arsenal for cancer treatment strategies.