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Effect of radiation energy and intracellular iron dose on iron oxide nanoparticle enhancement of radiation cytotoxicity

机译：辐射能和细胞内铁剂量对氧化铁纳米颗粒增强辐射细胞毒性的影响

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Iron oxide nanoparticles (IONPs) are one of several high-Z materials currently being investigated for their ability to enhance the cytotoxic effects of therapeutic ionizing radiation. Studies with iron oxide, silver, gold, and hafnium oxide suggest radiation dose, radiation energy, cell type, and the type and level of metallic nanoparticle are all critical factors in achieving radiation enhancement in tumor cells. Using a single 4 Gy radiation dose, we compared the level of tumor cell cytotoxicity at two different intracellular iron concentrations and two different radiation energies in vitro. IONPs were added to cell culture media at concentrations of 0.25 mg Fe/mL and 1.0 mg Fe/mL and incubated with murine breast adenocarcinoma (MTG-B) cells for 72 hours. Extracellular iron was then removed and cells were irradiated at either 662 keV or 10 MV. At the 0.25 mg Fe/mL dose (4 pg Fe/cell), radiation energy did not affect the level of cytotoxicity. However with 1.0 mg Fe/mL (9 pg Fe/cell), the higher 10 MV radiation energy resulted in 50% greater cytotoxicity as compared to cells without IONPs irradiated at this energy. These results suggest IONPs may be able to significantly enhance the cytotoxic effects of radiation and improve therapeutic ratio if they can be selectively associated with cancer cells and/or tumors. Ongoing in vivo studies of IONP radiation enhancement in a murine tumor model are too immature to draw conclusions from at this time, however preliminary data suggests similar effectiveness of IONP radiation enhancement at 6 MV and 18 MV energy levels. In addition to the IONP-based radiation enhancement demonstrated here, the use of tumor-localized IONP with an externally delivered, non-toxic alternating magnetic field affords the opportunity to selectively heat and kill tumor cells. Combining IONP-based radiation sensitization and heat-based cytotoxicity provides a unique and potentially highly effective opportunity for therapeutic ratio enhancement.
机译：氧化铁纳米颗粒（IONPs）是目前正在研究的几种高Z材料之一，这些材料具有增强治疗性电离辐射的细胞毒性作用的能力。对氧化铁，银，金和ha的研究表明，辐射剂量，辐射能量，细胞类型以及金属纳米粒子的类型和水平都是在肿瘤细胞中实现辐射增强的关键因素。使用单一的4 Gy辐射剂量，我们比较了两种不同细胞内铁浓度和两种不同辐射能在体外对肿瘤细胞的细胞毒性水平。将IONPs以0.25 mg Fe / mL和1.0 mg Fe / mL的浓度添加到细胞培养基中，并与鼠乳腺腺癌（MTG-B）细胞孵育72小时。然后去除细胞外铁，并以662 keV或10 MV照射细胞。在0.25 mg Fe / mL剂量（4 pg Fe /细胞）下，辐射能不影响细胞毒性水平。然而，与没有以该能量辐照IONP的细胞相比，在1.0 mg Fe / mL（9 pg Fe /细胞）的情况下，较高的10 MV辐射能量导致的细胞毒性提高了50％。这些结果表明，如果IONP可以与癌细胞和/或肿瘤选择性结合，它们可能能够显着增强放射线的细胞毒性作用并提高治疗率。正在进行的关于在鼠肿瘤模型中进行IONP辐射增强的体内研究尚不成熟，无法从此时得出结论，但是，初步数据表明，在6 MV和18 MV能量水平下IONP辐射增强的有效性相似。除了此处展示的基于IONP的辐射增强以外，将肿瘤定位的IONP与外部传递的无毒交变磁场配合使用还提供了选择性加热和杀死肿瘤细胞的机会。基于IONP的放射增敏和基于热的细胞毒性相结合，为提高治疗比率提供了独特且潜在的高效机会。

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