A Reactive Treatment: Using Non-Thermal Plasma Chemistry Against Cancer

Cancer remains one of the toughest challenges in medicine, especially in its late stages when tumours resist conventional treatments. But what if a specific kind of fluid – Plasma – could help doctors target cancer more precisely and with fewer side effects? THINK talks to researchers from the MIAPAM-CaT project, who are developing a new combination therapy to fight cancer.

In 2022, at a Xjenza information session, two researchers returned to a shared idea: using plasma (the fourth state of matter, consisting of ionised gas) as part of a cancer treatment. Prof. Byron Baron (Centre for Molecular Medicine and Biobanking) had previously explored the potential of plasma-activated fluids with a Japanese research group, and Dr Jefferson de Oliveira Mallia (Metamaterials Unit, Faculty of Science) was already involved in research on the antimicrobial and in vitro toxicology effects of non-thermal plasma. A few conversations and an undergraduate project later, the foundations of MIAPAM-CaT were laid.

Now supported by the Xjenza Fusion Research Excellence Programme, this project combines non-thermal plasma for activating liquid media with an intelligent molecular strategy to open new doors in cancer therapy – right from a small laboratory here in Malta.

Plasma-Activated Medium: The Basis of the Project

Plasma-activated medium (PAM) is a liquid that becomes chemically reactive when exposed to non-thermal plasma. The aim is to create a substance that can stress and damage cancer cells, without affecting healthy tissue. To produce PAM, researchers pass a noble gas, such as argon, through an electric field, creating a partially ionised state called a non-thermal plasma. When this plasma then interacts with the cell culture medium (a nutrient-rich liquid used for growing cells in laboratories), it produces a burst of short-lived reactive chemical species.

‘This interaction changes the chemical characteristics of the medium from its original form,’ says de O. Mallia. It transforms from a passive substance to one capable of disrupting the activity of cancer cells.

This disruption manifests as redox stress – an imbalance between the production and removal of reactive oxygen species within the body. Cancer cells, which divide rapidly and consume resources at a high rate, already live on the edge of oxidative stress. Introducing PAM pushes them over the edge. The reactive oxygen species it contains damage key proteins and cellular structures, overwhelming the cancer cells’ ability to cope.

Healthy cells divide more slowly and have more robust antioxidant systems, making them more resistant to this type of stress. That’s what makes PAM a promising candidate for targeting tumours with minimal side effects.

The Methylation Problem

But PAM alone is not enough, because cancer is a notoriously slippery opponent. Some tumours respond to oxidative stress by activating specific enzymes called methyltransferases (MTs). These enzymes modify proteins inside the cell, essentially helping the cancer resist cell death and continue to grow.

‘MTs boost cancer cells’ activity,’ explains Baron. ‘This allows the cells to overcome the effects induced by chemotherapeutic agents.’

The MIAPAM-CaT team hopes to overcome this by first using MT inhibitors – small molecules designed to block the activity of specific methyltransferases. This will weaken the cancer cells’ defences, allowing PAM to act more effectively. 

‘The idea is to treat the cancer cells first with the MT inhibitors and then treat with the PAM,’ says Baron. ‘By the time the cells try to avoid the cell death mechanisms, it’s already too late.’

Building It From Scratch

Towards a Smarter Therapy

The researchers are particularly interested in how this therapy might be applied to late-stage cancers, where tumours no longer respond to conventional treatments. By combining PAM with MT inhibitors, they hope to create a strategy that can disrupt cancer resistance mechanisms and provide a more targeted approach.

To achieve this, the next step for the MIAPAM-CaT team is to conduct detailed proteomic analyses, which involve studying the entire set of proteins in a cell. This will help them understand exactly how cells respond to treatment and identify any unexpected pathways or effects.

‘There’s still a lot about the cellular response that we don’t understand,’ says Baron. ‘Every bit of information we gather brings us one step closer, but more fundamental research is needed before this can move toward clinical use.’

More Than a Treatment

While the long-term goal of MIAPAM-CaT is clinical application, its impact could go much further. Having a reliable PAM production prototype at the University of Malta campus opens up new opportunities for research in oxidative stress responses and medical device development. But progress has not been easy.

Baron notes that the local research funding landscape makes it difficult to pursue early-stage, non-commercial science. ‘You need to produce a significant body of evidence to support the transition of an idea into a potential solution. Many projects may fail completely or fall short of the expected outcome. But it is still a step forward,’ he says.

For de O. Mallia and Baron, the MIAPAM-CaT project is about more than just the interdisciplinary fight against cancer – it’s about pushing the boundaries of what’s possible today in biomedical science through multidisciplinary approaches, even when resources are limited. ‘Our primary goal is to do research to generate new knowledge. If that results in a commercial product or solution, that’s great, but if it doesn’t, it could still help many researchers,’ Baron concludes.