# Dual-transferred atmospheric-pressure plasma jet modulates matrix metalloproteinase expression in breast cancer stem cells

## TL;DR

A new low-power plasma jet system effectively reduces breast cancer stem cell activity by suppressing genes linked to tumor spread.

## Contribution

A dual-transferred atmospheric-pressure plasma jet (DTAPPJ) system is introduced for targeted suppression of breast cancer stem cells via matrix metalloproteinase modulation.

## Key findings

- Helium-based DTAPPJ more effectively suppresses multiple MMP genes compared to argon.
- DTAPPJ reduces breast cancer stem cell viability and metabolic activity in a time- and gas-dependent manner.
- Gas-specific reactive oxygen and nitrogen species profiles drive the anticancer effects of DTAPPJ.

## Abstract

Breast cancer stem cells (BCSCs) are a highly aggressive subpopulation, driving tumor initiation, metastasis, and therapeutic resistance, largely through matrix metalloproteinases (MMPs)–mediated extracellular matrix remodeling. Here, we introduce a dual-transferred atmospheric-pressure plasma jet (DTAPPJ) platform designed to enhance plasma stability, reactive species delivery, and spatial controllability, enabling targeted modulation of BCSCs. The DTAPPJ system was evaluated using argon and helium as working gases, with direct plasma exposure for 120, 180, and 240 s. Voltage–power measurements confirmed stable plasma propagation and low energy consumption (<1 W). At the same time, optical emission spectroscopy revealed a sequential amplification of reactive oxygen and nitrogen species (RONS) across primary, secondary, and tertiary jets. Biologically, DTAPPJ exposure induced robust, time-dependent suppression of multiple MMP genes, including MMP-1, -2, -3, -7, -9, -10, −11, −13, and −14, with helium-driven plasma consistently outperforming argon. This repression correlated with significant reductions in BCSC viability and metabolic activity in the 3D culture system, highlighting the system's ability to overcome intrinsic antioxidant defenses. Mechanistically, DTAPPJ likely exerts its effects through the oxidative modulation of redox-sensitive transcription factors that regulate MMP expression, thereby collectively diminishing the invasive and metastatic potential. The dual-transfer architecture, incorporating floating copper electrodes, ensures safe operation, enhanced reactive species generation, and minimal thermal impact. Overall, our findings demonstrate that DTAPPJ represents a low-power, multi-targeted plasma modality capable of simultaneously suppressing MMP-mediated invasion and impairing BCSC viability, providing a promising strategy for translational anticancer applications and potential minimally invasive therapies.

Image 1

•DTAPPJ delivers stable, low-power plasma with rich RONS profiles from Ar and He gases.•Helium-based DTAPPJ consistently suppresses MMP genes more strongly than argon.•Prolonged exposure to DTAPPJ (240 s) maximizes the inhibition of MMPs transcript levels.•DTAPPJ markedly reduces BCSC viability in a time-dependent, gas-dependent manner.•Optical emission shows gas-specific RONS diversity driving DTAPPJ anticancer effects.

DTAPPJ delivers stable, low-power plasma with rich RONS profiles from Ar and He gases.

Helium-based DTAPPJ consistently suppresses MMP genes more strongly than argon.

Prolonged exposure to DTAPPJ (240 s) maximizes the inhibition of MMPs transcript levels.

DTAPPJ markedly reduces BCSC viability in a time-dependent, gas-dependent manner.

Optical emission shows gas-specific RONS diversity driving DTAPPJ anticancer effects.