Radiation therapy (RT) is the primary treatment for many
cancers, but its effectiveness is reduced due to radioresistance and side effects. The study aims to investigate an emerging treatment for
cancer, cold atmospheric plasma (CAP), as a selectable treatment between cancerous and healthy cells and its role in the occurrence of
photodynamic therapy (
PDT) utilizing
indocyanine green (ICG) as a
photosensitizer. We examined whether the efficiency of
radiotherapy could be improved by combining CAP with ICG. The
PDT effect induced by
cold plasma irradiation and the radiosensitivity of ICG were investigated on DFW and HFF cell lines. Then, for combined treatment, ICG was introduced to the cells and treated with
radiotherapy, followed by
cold plasma treatment simultaneously and 24-h intervals. MTT and colony assays were used to determine the survival of treated cells, and flow cytometry was used to identify apoptotic cells. Despite a decrease in the survival of
melanoma cells in CAP, ICG did not affect RT. Comparing the ICG + CAP group with CAP, a significant reduction in cell survival was observed, confirming the photodynamic properties of plasma utilizing ICG. The treatment outcome depends on the duration of CAP. The results for healthy and
cancer cells also confirmed the selectivity of plasma function. Moreover,
cold plasma sensitized
melanoma cells to
radiotherapy, increasing treatment efficiency. Treatment of CAP with RT can be effective in treating
melanoma. The inclusion of ICG results in plasma treatment enhancement. These findings help to select an optimal strategy for a combination of plasma and
radiotherapy.