University of Tehran Journal of Sciences, Islamic Republic of Iran 1016-1104 36 1 2025 01 01 Precision Tuning of a kHz-Driven Argon Plasma Jet Enables Dose-Controlled H₂O₂ Delivery to Overcome Chemoresistance in Colorectal Cancer 51 59 105960 10.22059/jsciences.2025.401773.1007952 EN Afshin Eftekharinasab Department of Physics and Institute for Plasma Research, Kharazmi University, Tehran, Islamic Republic of Iran Hassan Mehdian Department of Physics and Institute for Plasma Research, Kharazmi University, Tehran, Islamic Republic of Iran Ali Hasanbeigi Department of Physics and Institute for Plasma Research, Kharazmi University, Tehran, Islamic Republic of Iran Journal Article 2025 09 03 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, <em>p</em> < 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. https://jsciences.ut.ac.ir/article_105960_a671d4b5ac1cfbebb39a0062d1df0ffb.pdf