Feasibility study on the use of gold nanoparticles in fractionated kilovoltage X-ray treatment of melanoma

Purpose: Despite the high radioresistance of melanoma, unresectable lesions can be subjected to radiation treatment with the use of gold nanoparticles (AuNPs) as a dose-enhancing agent preferentially loaded on these lesions. The modality of single high-dose treatment has been investigated to confirm its therapeutic efficiency for AuNP-treated melanoma cells. This study explores the feasibility of utilizing AuNPs in fractionated radiation therapy of melanoma for further therapeutic gain. Materials and methods: The responses of human skin melanoma cells to 150-kVp X-ray exposure at 2 and 4 Gy were assessed by quantify gamma-H2AX expression and clonogenic survival, with or without 320 mu M of 50 nm AuNP treatment in a culture medium. The influence of AuNPs on cell cycle distribution was observed before irradiation and during 3 d period after irradiation. Results: The AuNP treatment of melanoma cells influenced the cellular response to kilovoltage X-rays to similar extents in terms of the percentage of gamma-H2AX-positive cells and the fractional loss of clonogenicity. Without radiation exposure, AuNPs reduced the portion of melanoma cells at the G(2)/M phase from 11 to 7%. After irradiation, the progression of the melanoma cells treated with AuNPs toward the G(2)/M phase was more rapid than that of the AuNP-free cells, and the release of the former from the G(2)/M phase was slower than that of the latter. At 24 h after irradiation with AuNPs, the cell cycle was rearranged in a pattern that increased the vulnerability of the cells to radiation damage. Conclusions: In addition to the benefit of AuNP treatment to the control of melanoma in single high-dose treatment, further therapeutic gain is expected through fractionated X-ray treatment that involves daily exposure. The AuNP-treated melanoma cells of an increased portion in the radiosensitive G(2)/M phase following a fractionated dose delivery would respond to the next treatment with an enhanced chance of clonogenic death.