Application of cold atmospheric plasma to medium generates “plasma-activated
medium” that induces apoptosis selectively in tumor cells and that has an antitumor effect in vivo. The underlying
mechanisms are not well understood.
Elucidation of potential chemical interactions within plasma-activated medium and of reactions of
medium components with specific target structures of tumor cells should allow to define the active principle in
plasma activated medium.
Established knowledge of intercellular apoptosis-inducing reactive oxygen/nitrogen species-dependent
signaling and its control by membrane-associated catalase and SOD was reviewed. Model experiments using
extracellular singlet oxygen were analyzed with respect to catalase inactivation and their relevance for the
antitumor action of cold atmospheric plasma. Potential interactions of this tumor cell-specific control system
with components of plasma-activated medium or its reaction products were discussed within the scope of the
reviewed signaling principles.
None of the long-lived species found in plasma-activated medium, such as nitrite and H2O2, nor OCl- or
.NO seemed to have the potential to interfere with catalase-dependent control of apoptosis-inducing signaling of
tumor cells when acting alone. However, the combination of H2O2 and nitrite might generate peroxynitrite. The
protonation of peroxnitrite to peroxynitrous acid allows for the generation of hydroxyl radicals that react with
H2O2, leading to the formation of hydroperoxide radicals. These allow for singlet oxygen generation and inactivation
of membrane-associated catalase through an autoamplificatory mechanism, followed by intercellular
Nitrite and H2O2 in plasma-activated medium establish singlet oxygen-dependent interference
selectively with the control system of tumor cells.
Over the past five years, the cold atmospheric plasma-activated solutions (PAS) have
shown their promissing application in cancer treatment. Similar as the common direct cold plasma treatment,
PAS shows a selective anti-cancer capacity in vitro and in vivo. However, different from the direct cold atmospheric
plasma (CAP) treatment, PAS can be stored for a long time and can be used without dependence on a
CAP device. The research on PAS is gradually becoming a hot topic in plasma medicine.
In this review, we gave a concise but comprehensive summary on key topics about PAS including
the development, current status, as well as the main conclusions about the anti-cancer mechanism achieved in
past years. The approaches to make strong and stable PAS are also summarized.
Conventional plasma jets for biomedical applications tend to have several drawbacks, such as high voltages, high gas delivery, large plasma probe volume, and the formation of discharge within the organ. Therefore, it is challenging to employ these jets inside a living organism’s body. Thus, we developed a single-electrode tiny plasma jet and evaluated its use for clinical biomedical applications. We investigated the effect of voltage input and flow rate on the jet length and studied the physical parameters of the plasma jet, including discharge voltage, average gas and subject temperature, and optical emissions via spectroscopy (OES). The interactions between the tiny plasma jet and five subjects (de-ionized (DI) water, metal, cardboard, pork belly, and pork muscle) were studied at distances of 10 mm and 15 mm from the jet nozzle. The results showed that the tiny plasma jet caused no damage or burning of tissues, and the ROS/RNS (reactive oxygen/nitrogen species) intensity increased when the distance was lowered from 15 mm to 10 mm. These initial observations establish the tiny plasma jet device as a potentially useful tool in clinical biomedical applications.
AbstractCholangiocarcinoma (CCA) is a rare biliary tract cancer with a low five-year survival rate and high recurrence rate after surgical resection. Currently treatment approaches include systemic chemotherapeutics such as FOLFIRINOX, a chemotherapy regimen is a possible treatment for severe CCA cases. A limitation of this chemotherapy regimen is its toxicity to patients and adverse events. There exists a need for therapies to alleviate the toxicity of a FOLFIRINOX regimen while enhancing or not altering its anticancer properties. Cold atmospheric plasma (CAP) is a technology with a promising future as a selective cancer treatment. It is critical to know the potential interactions between CAP and adjuvant chemotherapeutics. In this study the aim is to characterize the efficacy of FOLFIRINOX and CAP in combination to understand potential synergetic effect on CCA cells. FOLFIRINOX treatment alone at the highest dose tested (53.8 µM fluorouracil, 13.7 µM Leucovorin, 5.1 µM Irinotecan, and 3.7 µM Oxaliplatin) reduced CCA cell viability to below 20% while CAP treatment alone for 7 min reduced viability to 3% (p < 0.05). An analysis of cell viability, proliferation, and cell cycle demonstrated that CAP in combination with FOLFIRINOX is more effective than either treatment alone at a lower FOLFIRINOX dose of 6.7 µM fluorouracil, 1.7 µM leucovorin, 0.6 µM irinotecan, and 0.5 µM oxaliplatin and a shorter CAP treatment of 1, 3, or 5 min. In conclusion, CAP has the potential to reduce the toxicity burden of FOLFIRINOX and warrants further investigation as an adjuvant therapy.