Kim So-Ra, Kim Eun-Hee
a Radiation Bioengineering Laboratory, Department of Nuclear Engineering , Seoul National University , Seoul , Republic of Korea.
Int J Radiat Biol. 2018 Jan;94(1):8-16. doi: 10.1080/09553002.2018.1393579. Epub 2017 Nov 6.
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.
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.
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/M phase from 11 to 7%. After irradiation, the progression of the melanoma cells treated with AuNPs toward the G/M phase was more rapid than that of the AuNP-free cells, and the release of the former from the G/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.
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/M phase following a fractionated dose delivery would respond to the next treatment with an enhanced chance of clonogenic death.
尽管黑色素瘤具有高放射抗性，但对于不可切除的病灶，可使用优先负载于这些病灶上的金纳米颗粒（AuNP）作为剂量增强剂进行放射治疗。已对单次高剂量治疗方式进行研究，以确认其对经AuNP处理的黑色素瘤细胞的治疗效果。本研究探讨在黑色素瘤的分次放射治疗中利用AuNP以获得进一步治疗增益的可行性。
通过量化γ-H2AX表达和克隆形成存活率，评估人皮肤黑色素瘤细胞在有或无320 μM 50 nm AuNP处理的培养基中，接受2 Gy和4 Gy的150 kVp X射线照射后的反应。在照射前和照射后3天期间观察AuNP对细胞周期分布的影响。
就γ-H2AX阳性细胞百分比和克隆形成能力的分数损失而言，AuNP处理黑色素瘤细胞对千伏X射线的细胞反应影响程度相似。在无辐射暴露情况下，AuNP将黑色素瘤细胞处于G/M期的比例从11%降至7%。照射后，经AuNP处理的黑色素瘤细胞向G/M期进展比未处理细胞更快，且前者从G/M期释放比后者更慢。在用AuNP照射后24小时，细胞周期重新排列，增加了细胞对辐射损伤的易感性。
除了在单次高剂量治疗中AuNP处理对黑色素瘤控制的益处外，预计通过每日照射的分次X射线治疗可获得进一步的治疗增益。在分次剂量递送后，处于放射敏感G/M期的经AuNP处理的黑色素瘤细胞比例增加，对下一次治疗的反应将增加克隆性死亡的机会。
