Precision Tuning of a kHz-Driven Argon Plasma Jet Enables Dose-Controlled H₂O₂ Delivery to Overcome Chemoresistance in Colorectal Cancer

Document Type : Original Research Articles

Authors
Afshin Eftekharinasab
Hassan Mehdian
Ali Hasanbeigi
Department of Physics and Institute for Plasma Research, Kharazmi University, Tehran, Islamic Republic of Iran
10.22059/jsciences.2025.401773.1007952
Abstract
Colorectal cancer presents a significant therapeutic challenge, largely due to robust chemoresistance mechanisms, including the upregulation of antioxidant pathways. While cold atmospheric plasma is a promising anti-cancer modality, its efficacy can be limited by these cellular defenses. This study introduces a kilohertz AC-driven argon plasma jet with independently tunable voltage (1–20 kV) and frequency (18–28 kHz) as a novel platform for overcoming this resistance. We demonstrate that precision tuning of these electrical parameters allows for the controlled delivery of extracellular hydrogen peroxide (H₂O₂), a key long-lived reactive species. In the chemoresistant HT29 colorectal cancer cell line, we achieved a modulation of H₂O₂ concentrations in the culture medium, ranging from 291 to 371 µM. This H₂O₂ dosage showed a linear correlation with dose-dependent cytotoxicity (R² = 0.995, p < 0.001). Optimized parameters (10.5 kV, 28 kHz) overwhelmed the cells' redox defenses, reducing viability to 9.2% ± 3.6% after a 3-minute treatment. This approach successfully bypasses the Nrf2/Srx antioxidant pathway, which is known to confer resistance to helium plasma jets. Our findings establish that precisely controlling H₂O₂ delivery via a tunable argon plasma jet is a potent strategy for circumventing intrinsic chemoresistance in colorectal cancer, positioning this technology as a promising modality for precision oncology.
Keywords
Argon plasma jet
Colorectal cancer
Chemoresistance
Hydrogen peroxide (H₂O₂)
Subjects
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Journal of Sciences, Islamic Republic of Iran
Volume 36, Issue 1
Winter 2025
Pages 51-59