Atmospheric pressure plasma jets applied to cancerology: correlating electrical configurations with in vivo toxicity and therapeutic efficiency

Abstract

Two atmospheric pressure plasma jet devices - a plasma gun and a plasma Tesla jet - are compared in terms of safety and therapeutic efficiency to reduce the tumor volume progression of cholangiocarcinoma, i.e. a rare and very aggressive cancer emerging in biliary tree. For this, a three steps methodology is carried out. First, the two APPJ have been benchmarked in regard to their electrical and physico-chemical properties while interacting with material targets: dielectric plate, liquid sample, metal plate and an equivalent electrical circuit of human body. The propagation properties of the ionization wave interacting with these targets are discussed, in particular the profile of the related pulsed atmospheric plasma streams. In a second step, a dermal toxicity survey is performed so as to define an experimental operating window where plasma parameters can be changed without damaging healthy skin of mice during their exposure to plasma and without inducing any electrical hazards (burnings, ventricular fibrillation). Optimal conditions are identified discarding the conditions where slight alterations may be evidenced by histology (e.g. prenecrotic aspect of keratinocytes, alterations in the collagen structure). Hence, for the two APPJ plasma parameters these conditions are as follow: duty cycle=14 %, repetition frequency=30 kHz, magnitude=7 kV, gap=10 mm and exposure time=1 min. In a third step, the two plasma jets are utilized on cholangiocarcinoma xenograft tumor model developed in immunodeficient mice. The two devices are safe and a significant therapeutic efficiency is demonstrated with the plasma Tesla. In conclusion, we have developed a safe cold atmospheric plasma device with antitumoral properties in preclinical model of cholangiocarcinoma, opening the path for new anticancer treatment opportunities.