Cold Atmospheric Plasma for Selectively Ablating Metastatic Breast Cancer Cells

Mian Wang, Benjamin Holmes, Xiaoqian Cheng, Wei Zhu, Michael Keidar, PhD, Lijie Grace Zhang

Breast cancer is the second leading cause of cancer deaths in women. It is estimated that 232,340 new cases of invasive breast cancer will be diagnosed in the United States and 39,620 women will die of the disease in 2013, according to the American Cancer Society. Breast cancer exhibits an affinity to metastasize to bone, resulting in debilitating skeletal complications associated with significant morbidity and poor prognosis. Roughly, 85% of individuals eventually develop bone metastases in advanced breastcancer [1]. The growth of disseminated tumor cells in the skeleton requires tumor cells to inhabit the bone marrow wherein metastatic breast cancer cells colonize the skeleton and interrupt normal bone remodeling processes. Current breast cancer treatment options such as surgery and radiotherapy contain severe limitations with regards to nonselective and incomplete tumor ablation. Thus, new treatments which can completely and selectively ablate solid tumors and transient breast cancer cells and tissues while keeping surrounding healthy cells and tissues intact is highly desirable.

Plasma is an ionized medium that contains numerous active components including electrons and ions, free radicals, reactive molecules, and photons [2–4]. It can be categorized as either thermal or non-thermal plasma [4]. Thermal plasma has been widely used to modify material surfaces, which is generally conducted in a vacuum [5,6]. Cold atmospheric plasma (CAP), a non-thermal plasma, shows high electron temperatures but very low gas temperatures due to a weak ionization rate [5]. Because of the varied mass of CAP particles and constituents, thermodynamic equilibrium of electron self-collision occurs much faster than equilibrium between electrons and larger particles, such as ions [6,7]. Thus, the overall plasma temperature is much lower than the electron temperature, which is close to room temperature. As an emerging technique for biomedical applications, CAP exposure has been shown to be highly effective in germicidal and sterilization, wound healing, blood coagulation, material surface modifications and crosslinking and treatment of various diseases, including cancer [8–14]. In particular, CAP can potentially offer a minimally-invasive surgical approach allowing for specific cancer cell or tumor tissue removal without influencing surrounding healthy cells and tissues, thus making it a promising technology for cancer therapy. Two possible underlying mechanisms for CAP’s high selectivity towards cancer cells can be attributed to: (1) complex CAP composition and (2) the different nature of cancer cells and normal cells. Firstly, the variable cellular effects of CAP may be explained by the complex chemical composition of the CAP plume governed by the way the CAP is generated. Its presence can promote specific chemical reactions between charged particles and living cells triggering intracellular biochemical reactions that would elicit desired breast cancer therapeutic effects [15]. For example, reactive oxygen species (ROS, such as O, OH) are believed to be a major reason for cancer cell lysis [16] and bacterial inactivation [17], although the contribution of each type of the reactive species is still not well understood. In addition, the selective effects of CAP may be attributed to the significant difference of cancer cells and normal cells, thus rendering cancer cells more susceptible to CAP [18]. The objective of this research is to investigate a CAP-based therapy for the first time to selectively ablate metastatic breast cancer cell in metastatic bone site.