Plasma Activated Solutions and their Synergy with Radiation for Cancer Therapy

Abstract

Radiation therapy benefits nearly 50% of cancer patients, however there are patients for whom treatment fails. The application of radiosensitising agents to boost local effects to radioresistant cancers offers the potential to improve outcomes for these patients. An emerging radiosensitising agent is a Plasma Activated Liquid (PAL). PALs are generated when a liquid is exposed to a plasma, imparting the Reactive Oxygen and Nitrogen species (RONS) created during plasma activation. The ability of PAL to sensitise three different cell lines (hormone resistant prostate cancer DU 145, non-malignant prostate PNT1A and melanoma MM576) to ionising radiation was investigated in this thesis. First a custom underwater plasma treatment device was designed, built and optimised. Then the RONS output was characterised and calorimetry was developed as a method of dosimetry. The dose response relationships of both PAL and radiation were determined for each cell line, after which one concentration of PAL and one dose of ionising radiation was chosen for each cell line for combination therapy experiments. A synergy metric based upon the multiplicative survival principle was employed to assess the combination therapy experiments and found synergistic enhancement of radiation cytotoxicity for the DU 145 and the MM576 and found antagonistic reduction in radiation toxicity for the PNT1A.

While PAL and radiation were found to synergistically reduce cell survival using two methods of synergy metric evaluation regardless of the order of administration, application of PAL prior to irradiation is significantly more cytotoxic than when PAL is administered after radiation. When PAL was broken down into its major constituents, no statistical difference was found between the cytotoxicity from PAL, H2O2 alone and H2O2 with NO2-. These results provide compelling evidence for future studies in the use of H2O2 focused therapeutics to improve the response of radioresistant cancers to radiation therapy.