Abstract

Over the past decade, cold atmospheric plasmas have shown promising application in cancer therapy. The therapeutic use of plasma-activated media is a topic addressed in an emerging field known as plasma pharmacy. In oncology, plasma-activated media are used to harness the therapeutic effects of oxidant species when they come in contact with cancer cells. Among several factors that contribute to the anticancer effect of plasma-activated liquid media (PALM), H2O2 and NO derivatives likely play a key role in the apoptotic pathway. Despite the significant amount of literature produced in recent years, a full understanding of the mechanisms by which PALM exert their activity against cancer cells is limited. In this paper, a sealed dielectric-barrier discharge was used to disentangle the effect of reactive nitrogen species (RNS) from that of reactive oxygen species (ROS) on cancer cells. Two cancers characterized by poor prognosis have been investigated: metastatic melanoma and pancreatic cancer. Both tumour models exposed to PALM rich in H2O2 showed a reduction in proliferation and an increase in calreticulin exposure and ATP release, suggesting the potential use of activated media as an inducer of immunogenic cell death via activation of the innate immune system.

Highlights

  • In 1928, plasma was defined as the fourth state of matter: an ionized gas containing atoms, radicals, ions and molecules in ground and excited states, with an equal density of negative and positive particles[1]

  • Few papers in the literature show the use of dielectric-barrier discharges (DBDs) ignited in sealed systems; certain configurations use the liquid as part of the electrical system, with the counter electrode either submerged in the liquid or underneath the liquid separated by a barrier

  • The present paper investigates the effect of H2O2 and NO2− produced in the plasma on the survival of MM and PDAC cells and the role of these molecules in stimulating damage-associated molecular patterns (DAMPs) secretion from tested tumour cells

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Summary

Introduction

In 1928, plasma was defined as the fourth state of matter: an ionized gas containing atoms, radicals, ions and molecules in ground and excited states, with an equal density of negative and positive particles[1]. Evidence in the literature suggests that plasma-generated chemical reactive species are responsible for inducing certain cellular behaviours, plasma is composed of multiple effectors whose interaction with cells should not be overlooked. Active plasma species diffused in the liquid determine the nature and density of secondary species that, in turn, interact with cells and tissues[11]. Most papers on the remote treatment of liquids deal with plasma jet sources[16] The limits of these sources in this context are mainly the lack of homogeneity of the treatment when volumes higher than a few millilitres are to be treated, and the scant control of the chemical composition of the gas phase[17]. Few papers in the literature show the use of DBDs ignited in sealed systems; certain configurations use the liquid as part of the electrical system, with the counter electrode either submerged in the liquid or underneath the liquid separated by a barrier

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