Cold plasma penetrates deep into tumors and attacks cancer cells. Short-lived molecules were identified as key drivers.

Scientists at the Leibniz Institute for Plasma Science and Technology (INP), working with colleagues from Greifswald University Hospital and University Medical Centre Rostock, have shown that cold plasma can successfully destroy tumor cells even within deeper layers of tissue.

A key achievement of the project was the development of new tissue models, which allowed the team for the first time to study in detail how specific plasma components affect cancer cells.

What is cold plasma?

Plasma is an ionized gas that generates large numbers of chemically reactive molecules, collectively known as reactive oxygen and nitrogen species.

These highly short-lived molecules can strongly influence biological activity, including processes that determine whether tumor cells survive or die.

New tissue models provide important insights

"The effect of plasma in tissue is very complex and little understood. We have therefore developed a 3D model made of hydrogels that mimics real tumor tissue. In this model, we were able to observe exactly how deep the molecules from the plasma penetrate – and which of these molecules are important for the effect on tumor cells," explains Lea Miebach, first author of the study.

Particularly short-lived molecules such as peroxynitrite penetrated several millimeters deep into the tissue. Hydrogen peroxide, which had previously been considered the main active ingredient in laboratory research, showed little effect: even when it was specifically removed, the effect of the plasma remained strong.

Use during surgery is also conceivable

Another model investigated how well plasma could work in the follow-up treatment of tumor surgery. Residual tumor cells at the edge of an artificial surgical wound were specifically treated with plasma.

The result: here too, a strong effect was observed, especially in cells that had already spread into the surrounding tissue. These findings could help to better prevent relapses after surgery.

Important step for plasma medicine

"Our results could significantly improve the medical application of plasma," says Prof. Dr. Sander Bekeschus, head of the Plasma Medicine research program at INP. "The better we understand which molecules are active in the tissue, the more precisely plasma devices can be used for specific types of cancer."

The work was carried out using the medically approved plasma jet "kINPen." In the long term, the method could help make therapies more effective and gentler.

Reference: "Gas plasma technology mediates deep tissue and anticancer events independently of hydrogen peroxide" by Lea Miebach, Marten Hagge, Alice Martinet, Debora Singer, Nadine Gelbrich, Stephan Kersting and Sander Bekeschus, 31 July 2025, Trends in Biotechnology.
DOI: 10.1016/j.tibtech.2025.07.004

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