Northern Ireland Cancer Centre, Queen's University, Belfast, Northern Ireland.
Int J Radiat Oncol Biol Phys. 2011 Feb 1;79(2):531-9. doi: 10.1016/j.ijrobp.2010.08.044. Epub 2010 Nov 20.
Gold nanoparticles (GNPs) have been shown to cause sensitization with kilovoltage (kV) radiation. Differences in the absorption coefficient between gold and soft tissue, as a function of photon energy, predict that maximum enhancement should occur in the kilovoltage (kV) range, with almost no enhancement at megavoltage (MV) energies. Recent studies have shown that GNPs are not biologically inert, causing oxidative stress and even cell death, suggesting a possible biological mechanism for sensitization. The purpose of this study was to assess GNP radiosensitization at clinically relevant MV X-ray energies.
Cellular uptake, intracellular localization, and cytotoxicity of GNPs were assessed in normal L132, prostate cancer DU145, and breast cancer MDA-MB-231 cells. Radiosensitization was measured by clonogenic survival at kV and MV photon energies and MV electron energies. Intracellular DNA double-strand break (DSB) induction and DNA repair were determined and GNP chemosensitization was assessed using the radiomimetic agent bleomycin.
GNP uptake occurred in all cell lines and was greatest in MDA-MB-231 cells with nanoparticles accumulating in cytoplasmic lysosomes. In MDA-MB-231 cells, radiation sensitizer enhancement ratios (SERs) of 1.41, 1.29, and 1.16 were achieved using 160 kVp, 6 MV, and 15 MV X-ray energies, respectively. No significant effect was observed in L132 or DU145 cells at kV or MV energies (SER 0.97-1.08). GNP exposure did not increase radiation-induced DSB formation or inhibit DNA repair; however, GNP chemosensitization was observed in MDA-MB-231 cells treated with bleomycin (SER 1.38).
We have demonstrated radiosensitization in MDA-MB-231 cells at MV X-ray energies. The sensitization was cell-specific with comparable effects at kV and MV energies, no increase in DSB formation, and GNP chemopotentiation with bleomycin, suggesting a possible biological mechanism of radiosensitization.
金纳米颗粒（GNPs）已被证明会导致千伏（kV）辐射致敏。金与软组织之间的吸收系数差异，作为光子能量的函数，预测在千伏（kV）范围内会出现最大增强，而在兆伏（MV）能量下几乎没有增强。最近的研究表明，GNPs 并非生物惰性的，会导致氧化应激甚至细胞死亡，这表明致敏作用可能存在生物学机制。本研究旨在评估在临床相关的 MV X 射线能量下 GNP 的放射增敏作用。
在正常 L132、前列腺癌 DU145 和乳腺癌 MDA-MB-231 细胞中评估 GNPs 的细胞摄取、细胞内定位和细胞毒性。通过在 kV 和 MV 光子能量以及 MV 电子能量下的集落形成存活来测量放射增敏作用。测定细胞内 DNA 双链断裂（DSB）诱导和 DNA 修复，并使用放射模拟剂博来霉素评估 GNP 化学增敏作用。
所有细胞系均发生了 GNP 摄取，MDA-MB-231 细胞摄取量最大，纳米颗粒积聚在细胞质溶酶体中。在 MDA-MB-231 细胞中，分别使用 160 kVp、6 MV 和 15 MV X 射线能量，实现了放射增敏增强比（SER）为 1.41、1.29 和 1.16。在 kV 或 MV 能量下，L132 或 DU145 细胞中未观察到明显的作用（SER 0.97-1.08）。GNP 暴露并未增加辐射诱导的 DSB 形成或抑制 DNA 修复；然而，在用博来霉素处理的 MDA-MB-231 细胞中观察到 GNP 化学增敏作用（SER 1.38）。
我们已经证明了在 MV X 射线能量下 MDA-MB-231 细胞的放射增敏作用。这种增敏作用是细胞特异性的，在 kV 和 MV 能量下具有相似的作用，DSB 形成没有增加，并且与博来霉素联合使用时 GNP 化学增敏作用增强，这表明放射增敏作用可能存在生物学机制。
