Anti-Cancer Strategy: Combining Cold Atmospheric Plasma with Theranostic Nanoparticles

Plasma constitutes ninety-nine percent of all normal matter in the universe and is a fascinating form of matter. It is a gaseous-like medium containing ions, free electrons, photons, and electromagnetic fields, which exhibit varied behavior. Artificial plasma, especially thermal plasma, has been studied for decades and applied in various fields. More recently, cold atmospheric plasma (CAP) emerged as a cutting-edge technology in biomedicine. CAP can safely operate on human tissue at room temperature and atmospheric pressure, creating a unique environment with reactive oxygen and nitrogen species (RONS), electrons, and neutral particles that induce biological effects.

CAP was explored as a novel intervention for cancer therapy, specifically used as a palliative treatment in patients. However, its widespread adoption faced challenges related to precise delivery, diffusion into tumors, and real-time diagnosis during treatment. Glioblastoma multiforme (GBM), the most aggressive brain cancer, showed resistance to traditional interventions.

In my doctoral study at TU Dublin, it was demonstrated for the first time that CAP stimulated membrane-repair endocytosis and the uptake of nanoparticles into cell lines, inducing significant synergistic cytotoxicity. This project further refined this therapeutic pathway by combining it with RONS-activated therapeutic pro-drugs and diagnostic fluorophores carried by pH-sensitive nanoparticles. This approach, known as CAP-triggered theranostics, aimed to ensure targeted delivery and activation of cytotoxicity while enabling real-time monitoring of treatment efficacy using RONS-activated diagnostic agents.

The project tested the delivery and efficacy of CAP-triggered theranostics in mixed cultures, three-dimensional cell spheroids, and blood-brain barrier models.