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

SIMPLE SUMMARY: During the last decade, cold atmospheric plasmas (CAP) have been broadly investigated for their therapeutic effect against cancer. CAP sources can be used to treat liquid media, thereby generating plasma-conditioned liquids (PCL). PCL represent a very interesting alternative to direct CAP treatment, because they may allow treatment of malignant tumors located in inner organs of the body by means of an injection, thus avoiding multiple surgeries. Although research on this therapy is still in its early stage, PCL have already demonstrated their potential anticancer effect in different types of cancer in vivo. This review gathers the existing literature involving PCL treatments in vivo, highlighting the differences between the approaches undertaken and the need for establishing standardized protocols in order to better understand the effects of PCL-based therapies in vivo. 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.