Atkinson Jake, Chopin Joshua, Bezak Eva, Le Hien, Kempson Ivan
Future Industries Institute, University of South Australia, Mawson Lakes, SA, 5095, Australia.
Industrial AI Research Centre, University of South Australia, Mawson Lakes, SA, 5095, Australia.
Chemphyschem. 2025 Feb 1;26(3):e202400764. doi: 10.1002/cphc.202400764. Epub 2024 Nov 21.
Metal nanoparticles sensitize cancers to radiotherapy however their mechanisms of action are complex. The conceptual inspiration arose from theories of physical dose deposition however various chemical and biological factors have also been identified. Interpretation of data has been limited by challenges in measuring true DNA damage compared to DNA damage repair factors. Here, we applied a new assay, STRIDE, for the first time to measure DNA double strand breaks (DSBs) in 4T1 cells as a model of triple negative breast cancer exposed to gold nanoparticles and radiation, and compared this to the common γH2AX assay for DSB repair. The STRIDE assay showed no increase in DSB detection 15 mins after irradiation for cells containing nanoparticles compared to cells without. Gold nanoparticles led to prolonged detection of DSBs after irradiation and delayed the DSB repair. The data show no evidence of increased radiation dose deposition with nanoparticles, but rather enhanced radiobiological effects resulting from nanoparticles which includes disruption of the recruitment of essential DDR machinery, thereby impairing DNA repair processes.
金属纳米颗粒可使癌症对放射治疗敏感，但其作用机制复杂。概念灵感源自物理剂量沉积理论，不过也已确定了各种化学和生物学因素。与DNA损伤修复因子相比，在测量真正的DNA损伤方面存在挑战，这限制了对数据的解读。在此，我们首次应用一种新的检测方法STRIDE来测量4T1细胞中的DNA双链断裂（DSB），4T1细胞作为三阴性乳腺癌的模型，使其暴露于金纳米颗粒和辐射下，并将此与用于DSB修复的常见γH2AX检测方法进行比较。STRIDE检测显示，与不含纳米颗粒的细胞相比，含纳米颗粒的细胞在照射后15分钟时DSB检测结果未增加。金纳米颗粒导致照射后DSB检测时间延长，并延迟了DSB修复。数据表明，没有证据显示纳米颗粒会增加辐射剂量沉积，而是纳米颗粒增强了放射生物学效应，其中包括破坏了关键DDR机制的募集，从而损害了DNA修复过程。
