Time-Resolved Oxygen Dynamics Reveals Redox-Selective Apoptosis Induced by Cold Atmospheric Plasma in HT-29...

Area of Science:

• Biophysics
• Biochemistry
• Oncology

Background:

• Cold atmospheric plasma (CAP) shows promise for cancer treatment due to selective malignant cell elimination.
• The Bauer theory proposes that plasma-derived hydrogen peroxide (H2O2) and nitrite (NO2-) synergistically generate singlet oxygen (1O2), inactivating catalase and enabling a self-amplifying cycle for cancer cell death.

Purpose of the Study:

• To investigate the role of singlet oxygen (1O2) and extracellular dissolved oxygen (DO) dynamics in cold atmospheric plasma (CAP) induced cancer cell death.
• To provide mechanistic validation for the Bauer redox model of CAP anticancer selectivity.

Main Methods:

• Utilized time-resolved phosphorescence lifetime spectroscopy to monitor extracellular DO in HT-29 colorectal cancer cells treated with an argon plasma jet.
• Employed intracellular reactive oxygen species (ROS) imaging to correlate ROS levels with cell viability and extracellular 1O2 dynamics.

Main Results:

• Observed a delayed surge in extracellular 1O2 specifically in dying cancer cells between 10-20 minutes post-CAP treatment, aligning with the Bauer model's predictions.
• Demonstrated a strong correlation between intracellular ROS, extracellular 1O2 dynamics, and loss of cancer cell viability.
• Confirmed that temporal DO variations reflect the combined effects of rapid 1O2 production and cellular reactions.

Conclusions:

• Mechanistically validated the Bauer redox model for CAP-induced cancer cell death.
• Established early oxygen dynamics following CAP exposure as potential predictive biomarkers for treatment efficacy in plasma and photodynamic therapies.