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Plasma Medicine
SJR: 0.271 SNIP: 0.316 CiteScore™: 1.9

ISSN Print: 1947-5764
ISSN Online: 1947-5772

Plasma Medicine

DOI: 10.1615/PlasmaMed.2017019883
pages 283-297

Nanosecond-Pulsed Dielectric Barrier Discharge–Induced Antitumor Effects Propagate through Depth of Tissue via Intracellular Signaling

Pietro Ranieri
Department of Nuclear Engineering and Radiological Science, University of Michigan, Ann Arbor, MI
R. Shrivastav
Drexel University, C. & J. Nyheim, Camden, NJ 08103
M. Wang
Drexel University, C. & J. Nyheim, Camden, NJ 08103
Abraham Lin
University of Antwerp, Department of Chemistry, Antwerp, Belgium
Gregory Fridman
C&J Nyheim Plasma Institute, Drexel University, Camden, New Jersey 08103
Alexander A. Fridman
C&J Nyheim Plasma Institute, Drexel University, Camden, New Jersey 08103
L.-H. Han
Drexel University, C. & J. Nyheim, Camden, NJ 08103
Vandana Miller
C&J Nyheim Plasma Institute, Drexel University, Camden, New Jersey 08103


Studies using xenograft mouse models have shown that plasma applied to the skin overlying tumors results in tumor shrinkage. Plasma is considered a nonpenetrating treatment; however, these studies demonstrate plasma effects that occur beyond the postulated depth of physical penetration of plasma components. The present study examines the propagation of plasma effects through a tissue model using three-dimensional, cell-laden extracellular matrices (ECMs). These ECMs are used as barriers against direct plasma penetration. By placing them onto a monolayer of target cancer cells to create an in-vitro analog to in-vivo studies, we distinguished between cellular effects from direct plasma exposure and cellular effects due to cell-to-cell signaling stimulated by plasma. We show that nanosecond-pulsed dielectric barrier discharge plasma treatment applied atop an acellular barrier impedes the externalization of calreticulin (CRT) in the target cells. In contrast, when a barrier is populated with cells, CRT externalization is restored. Thus, we demonstrate that plasma components stimulate signaling among cells embedded in the barrier to transfer plasma effects to the target cells.

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