Plasma-Conditioned Liquids as Anticancer Therapies In Vivo: Current State and Future Directions

Abstract

Plasma-conditioned liquids (PCL) are gaining increasing attention in the medical field, especially in oncology, and translation to the clinics is advancing on a good path. This emerging technology involving cold plasmas has great potential as a therapeutic approach in cancer diseases, as PCL have been shown to selectively kill cancer cells by triggering apoptotic mechanisms without damaging healthy cells. In this context, PCL can be injected near the tumor or intratumorally, thereby allowing the treatment of malignant tumors located in internal organs that are not accessible for direct cold atmospheric plasma (CAP) treatment. Therefore, PCL constitutes a very interesting and minimally invasive alternative to direct CAP treatment in cancer therapy, avoiding surgeries and allowing multiple local administrations. As the field advances, it is progressively moving to the evaluation of the therapeutic effects of PCL in in vivo scenarios. Exciting developments are pushing forward the clinical translation of this novel therapy. However, there is still room for research, as the quantification and identification of reactive oxygen and nitrogen species (RONS) in in vivo conditions is not yet clarified, dosage regimens are highly variable among studies, and other more relevant in vivo models could be used. In this context, this work aims to present a critical review of the state of the field of PCL as anticancer agents applied in in vivo studies.

Keywords: cancer; cold atmospheric plasma; in vivo; plasma-conditioned liquids.

Figure 1

Tumor formation strategies on mice models for PCL treatments in vivo. (A) Current approaches assessed in the formation of tumors in animals for PCL treatments in vivo. (B) Possible future directions in the generation of tumors in mice for the study of PCL treatments in vivo, which involve (B.i) patient derived xenografts, (B.ii) genetically engineered mice models, and (B.iii) humanized mice models.

Figure 2

Three different kinds of liquids were used to generate PCL for in vivo assays.

Figure 3

Possible methods available for tumor monitoring and biological molecular analysis to monitor and evaluate the effectiveness of PCL treatments in vivo. (A) Analysis applicable for tumor monitoring in vivo; (B) Biological and molecular analysis for ex vivo tumor analysis

Figure 4

Schematic illustration of subcutaneous and peritoneal administration of PCL, including the percentage of the studies that used each route of administration to treat tumors in vivo with PCL.