Cold Atmospheric Plasma (CAP) is a near-room-temperature partially ionized gas, composed of reactive oxygen and nitrogen species. CAP also generates physical factors, including ultraviolet irradiation, thermal emission, and an electromagnetic (EM) effect. The multimodal chemical and physical nature of CAP makes it a suitable, controllable, flexible, and even a self-adaptive tool for many medical and biological applications, ranging from microorganism sterilization, dermatitis, wound healing, and cancer therapy. It is promising that CAP could help to mitigate the COVID 19 pandemic by effectively inactivating the SARS-CoV-2 virus on diverse surfaces.
Biological killing is a foundation to understand these applications. Reactive species and their radical effects are the foundation to cause the CAP-based biological destruction in most cases. Basically, plasma medicine has even been regarded as a reactive species-based medicine. Here, we provide a systematic introduction and critical summary of the entire picture of biological killing due to CAP treatment and corresponding mechanisms based on the latest discoveries. This work provides guiding principles for diverse applications of CAP in modern biotechnology and medicine.
CAP is a near-room-temperature ionized gas composed of products including neutral particles, such as neutral atoms and molecules; charged particles, such as ions; electrons; and diverse, long-lived and short-lived reactive species, such as reactive oxygen species (ROS) and reactive nitrogen species (RNS) . CAP is also referred to as nonthermal plasma (NTP), cold plasma, physical plasma, and gas plasma in many references . CAP is a non-equilibrium plasma in which heavy particles have effective temperatures close to room temperature through weak elastic collisions during the discharge process . CAP also generates several physical effects, including thermal effect, UV effect, and EM effect .
Three types of CAP sources have been widely used in plasma medicine and can be roughly divided into three categories: direct discharge sources, indirect discharge sources, and hybrid discharge sources . Despite different morphologies, power input, and reactive species generation in CAP, their chemical composition and physical effects are quite similar. CAP can be precisely controlled by modulating basic operational parameters (gas flow rate, etc.) and discharge parameters (such as discharge voltage, current, duty circle, etc.) .
Plasma generated by these sources can be used to directly touch biological samples, which exposes samples to reactive species and physical factors. Alternatively, biological adaptive solutions, such as medium and phosphate-buffered saline (PBS), can be used as a carrier of these long-lived reactive species to exert a killing effect on viruses and cells . Reactive species will cause oxidative stress in the CAP-treated cells and trigger cell-death pathways if the reactive species’ dose on a single cell is sufficiently large . The biological effects of physical factors have been hypothesized for a long time but without clear evidence until very recently. One possible candidate is the EM effect from CAP jet, which causes structural damage on melanoma cells and triggers quick necrosis .
The multimodal chemical and physical nature of CAP makes it a suitable, controllable, flexible, and even a self-adaptive tool for many medical applications, ranging from microorganism sterilization, dermatitis, wound healing, and cancer therapy. For microorganism sterilization, particularly bacterial inactivation, CAP can cause strong damage on both gram-positive and gram-negative bacteria, including some multi-drug resistant bacteria . The biofilm composed of a complex microorganism community can also be effectively inactivated by CAP treatment . These anti-bacterial capacities of CAP may be a foundation to drastically improve wound healing efficacy . Over the past decade, CAP has shown impressive potential as a novel anti-cancer tool both in vitro and in vivo. CAP can selectively kill many cancer cell lines while having only limited side effects on normal counteracting cell lines . Importantly, a simple CAP treatment just on the skin above the subcutaneous tumor site could effectively decrease the tumor size and extend life in mice, which demonstrates the non-invasive potential of CAP as a novel anti-cancer modality . Besides, the inactivation of viruses by CAP has also been reported in many studies and has recently been summarized . The CAP-triggered cell death or virus inactivation is the foundation of nearly all these applications (Figure 1).
Figure 1. A schematic illustration of biological killing by CAP.
This entry is adapted from 10.3390/biomedicines9091259