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

Abstract

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 μM 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 G₂/M phase from 11 to 7%. After irradiation, the progression of the melanoma cells treated with AuNPs toward the G₂/M phase was more rapid than that of the AuNP-free cells, and the release of the former from the G₂/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 G₂/M phase following a fractionated dose delivery would respond to the next treatment with an enhanced chance of clonogenic death.

Keywords:

• Gold nanoparticle
• fractionated radiation therapy
• melanoma
• therapeutic gain

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the contents and writing of the article.

Notes on contributors

Dr. So-Ra Kim, received her Ph.D. degree in Nuclear Engineering from Seoul National University. She is currently a senior research scientist in Nuclear Environmental Safety Research Division at the Korea Atomic Energy Research Institute. Her research focus is on the nuclear environmental safety assessment and radiological dose assessment.

Professor Eun-Hee Kim, is a nuclear engineer with a specialty in radiation protection. She explores new approaches in irradiation setups for radiation biology experiments. Her research team has built an electron microbeam irradiation system, a hard X-ray irradiation facility, and an alpha irradiator for its own research purposes.

Additional information

Funding

This work was supported by Basic Research Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT and Future Planning (No. 2010-0021827).