Miao Qi

Brain diseases such as ischaemic stroke, Alzheimer’s disease (AD), and glioma were characterized by high mortality and disability rate, and oxidative stress remains a major obstacle in treatment. Plasma–nanomedicine synergistic treatment technology provides a very attractive treatment strategy based on complementarity. This technology integrates cold atmospheric plasma (CAP) with nanomedicine. CAP produces active substances that regulate oxidative stress, while nanomedicine is specially designed for targeted delivery, controlled release, and microenvironmentally responsive activation of therapeutic agents. This integration generates new therapeutic functions and significantly improves the overall therapeutic effect. Despite the broad prospects of this emerging technology, researchers in the fields of medicine, physics, or pharmacy have not yet paid much attention to it. To fill this research gap, this review describes the physicochemical properties and biological effects of CAP and summarizes the latest advances in plasma nanomedicine strategies in the field of brain disease intervention, and reviews the four major nanomedical categories—metal-based, inorganic non-metallic, polymer-based and hydrogel systems—and their clinical applications in the treatment of brain tumors, strokes and neurodegenerative diseases in conjunction with CAP. Finally, we highlight a number of key challenges—limited resources of special CAP equipment, incomplete understanding of the mechanism, obstacles to transformation application—and put forward the future research direction to promote the development of accurate, safe, and clinical transformation value plasma–nanomedicine therapy for brain diseases.

Cancer remains a significant global public health concern. Numerous challenges still remain in its treatment. Recently, a novel two-dimensional material—violet phosphorene nanosheets (VPNS)—has shown considerable application potential in the biomedical field due to its unique physicochemical properties. The VPNS with a concentration of 41.00 μg/mL has been demonstrated to exhibit significant anti-cancer effects through the induction of apoptosis. The treatment of VPNS was revealed by cell metabolomics analysis to a marked down-regulation of succinate hemialdehyde expression and an up-regulation of pyridoxine levels in cancer cells. These differentially expressed metabolites are closely associated with the vitamin B6 metabolic pathway. In addition, the VPNS has also been demonstrated to exert excellent anti-cancer effects within a living organism by in vivo animal experiments.

Multiple myeloma (MM) is the second most common hematologic malignancy. MM stem cells (MMSCs) are thought to be the main causes of in vivo engraftment and eventual recurrence. As a notable new technology, cold atmospheric plasmas (CAPs) show a promising anti-tumor effect, due to their production of various ROS. In this study, we found that different types of plasma could inhibit MM’s ability to form cell colonies, suppress MM in vivo engraftment, and extend survival times. We demonstrated that NAC (a ROS scavenger) could block ROS increases and reverse the inhibition of MM’s cell-colony-formation ability, which was induced by the plasma treatment. By using a stem cell signaling array, we found that the Notch pathway was inhibited by the plasma treatment; this was further confirmed by conducting real-time PCRs of three MM cell lines. Together, these results constitute the first report of plasma treatment inhibiting MM in vivo engraftment and prolonging survival time by suppressing the Notch pathway via ROS regulation.

In recent years, the emerging technology of cold atmospheric pressure plasma (CAP) has grown rapidly along with the many medical applications of cold plasma (e.g., cancer, skin disease, tissue repair, etc.). Plasma-activated liquids (e.g., culture media, water, or normal saline, previously exposed to plasma) are being studied as cancer treatments, and due to their advantages, many researchers prefer plasma-activated liquids as an alternative to CAP in the treatment of cancer. In this study, we showed that plasma-activated-saline (PAS) treatment significantly inhibited tumor growth, as compared with saline, in melanoma, and a low-pH environment had little effect on tumor growth in vivo. In addition, based on an ultra-high-performance liquid tandem chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) analysis of tumor cell metabolism, the glycerophospholipid metabolic pathway was the most susceptible metabolic pathway to PAS treatment in melanoma in vitro and in vivo. Furthermore, PAS also inhibited cell proliferation in vivo in oral tongue squamous-cell cancer and non-small-cell lung cancer. There were few toxic side effects in the three animal models, and the treatment was deemed safe to use. In the future, plasma-activated liquids may serve as a potential therapeutic approach in the treatment of cancer.

Terahertz is a new radiation source with many unique advantages. In recent years, its application has rapidly expanded to various fields, but there are few studies on the individual effects of terahertz. In this study, we investigated the behavioral effects of terahertz radiation on C57BL/6 mice, and we conducted an open field test, an elevated plus maze test, a light–dark box test, a three-chamber social test, and a forced swim test to explore the effects of terahertz radiation on mice from a behavioral perspective. The results show that terahertz wave may increase anti-anxiety, anti-depression, and social interaction in mice.

Infection can hinder the process of wound healing, so it is important to begin antibacterial treatment quickly after a wound forms. Plasma activated water (PAW) can inactivate a variety of common wound infection bacteria. In this study, we compared the effects of PAW prepared with portable surface discharge plasma equipment and medical alcohol on wound healing in a mouse full-thickness skin wound model. The effectiveness of wound healing processes in mice was ranked accordingly: PAW treatment group > medical alcohol treatment group > control group. In order to further understand the mechanism of PAW in promoting wound healing, we tested the expression levels of the pro-inflammatory factors interleukin (IL)-1β and IL-6, the anti-inflammatory factor IL-10, and vascular endothelial growth factor (VEGF). The results showed that PAW promoted the release of pro-inflammatory factors and anti-inflammatory factors from the wounds in mice, which allowed the mice in the treatment group to transition out of the inflammatory period early and enter the next stage of wound healing. The expression level of VEGF in the wounds of mice in the PAW treatment group was higher, which indicates that the microvessels around the wound in the PAW treatment group proliferated faster, and thus the wound healed faster. PAW biosafety experiments showed that PAW did not significantly affect the appearance, morphology, or tissue structure of internal organs, or blood biochemical indicators in mice. In general, PAW prepared via portable devices is expected to become more widely used given its convenience, affordability, and lack of side effects in promoting wound healing.