Cold Atmospheric Plasma as a Selective Strategy for Targeted Cancer Cell Apoptosis: Integrating Plasma Physics with Molecular Oncology

Abstract

Cold Atmospheric Plasma (CAP) is a recent and exciting non-thermal technology with great promise in precision oncology as it can selectively trigger apoptosis of malignant cells while mostly sparing normal tissues. In this review, we cover the physical and biological mechanisms for CAP-induced anticancer activity focusing on synergistic action of plasma-treated reactive oxygen and nitrogen species (RONS), transient electric fields, ultraviolet photons or charged particles. These plasma/blood-derived components disrupt intracellular redox homeostasis, promote mitochondrial dysfunctions, induce DNA damages and activate the intrinsic/ extrinsic apoptotic pathways in cancer cells. It discusses the biological base of CAP selectivity through many characteristics, such as increased basal oxidative stress and changes in the composition of membranes which classically exist for malignant cells; mitochondrial alterations associated with malignancy; failure of antioxidant defense systems. This review also provides a summary of recent advances in this field, including plasma-activated liquids (PALs), nanotechnology-assisted delivery systems, immune-modulatory effects and combination therapies. We outline challenges in plasma dosimetry, device standardization, treatment reproducibility and long-term clinical safety. In conclusion, CAP provides a cross-disciplinary treatment paradigm bridging diverse fields within plasma physics, chemistry and molecular biology with the oncology domain. Although strong experimental evidence demonstrates its effects as an anticancer modality, it requires further large scale preclinical and clinical studies before CAP can be adopted clinically for use in precision cancer medicine.