Bromma Kyle, Beckham Wayne, Chithrani Devika B
Department of Physics and Astronomy, University of Victoria, Victoria, BC Canada.
British Columbia Cancer, Victoria, BC Canada.
Cancer Nanotechnol. 2023;14(1):80. doi: 10.1186/s12645-023-00231-5. Epub 2023 Oct 19.
Much in vitro research on the applicability of gold nanoparticles (GNPs) in cancer treatment has been focused on two-dimensional (2D) monolayer models. To improve this, we explored the effect of the combination of GNPs and docetaxel (DTX) with radiotherapy (RT) in a more complex three-dimensional (3D) spheroid that can better mimic a real tumour microenvironment.
Two cell lines, prostate cancer LNCaP and cervical cancer HeLa, were grown in monolayer and spheroids. Cells were dosed with GNPs at a concentration of 10 and with DTX at a dose that inhibited growth-rate by 50%. Samples were irradiated 24 h after drug dosing with 2 Gy, 5 Gy, or 10 Gy using a 6 MV beam. Monolayer cells had the DNA double-strand breaks (DSBs) probed 24 h post-radiation, and cell proliferation observed over 7 days. Spheroid proliferation was monitored over 14 days along with spheroid volume measurements.
In DTX and GNP-treated monolayer samples, there is decreased survival after irradiation with 5 and 10 Gy of 16-24% and an increase in DSBs of 91.6-109.9%, compared to DTX. In spheroids, GNPs decreased the surviving cells by 10.54-15.61% compared to control, while GNPs and DTX decreased survival by 20.9-31.04%. There is reduced spheroid volume 14 days after treatment with the triple combination.
Combining GNPs and DTX leads to a synergistic radiosensitization effect in spheroids, which can better mimic the tumour microenvironment. Testing treatment modalities with spheroids and RT may allow a quicker translation to the clinic.
The online version contains supplementary material available at 10.1186/s12645-023-00231-5.
关于金纳米颗粒（GNP）在癌症治疗中适用性的许多体外研究都集中在二维（2D）单层模型上。为了改进这一点，我们在更复杂的三维（3D）球体模型中探索了GNP与多西他赛（DTX）联合放疗（RT）的效果，该模型能够更好地模拟真实的肿瘤微环境。
将前列腺癌LNCaP和宫颈癌HeLa这两种细胞系培养成单层和球体。细胞分别用浓度为10的GNP和抑制生长率50%的剂量的DTX处理。给药24小时后，使用6兆伏射线束分别以2戈瑞、5戈瑞或10戈瑞对样品进行照射。对单层细胞在辐射后24小时检测DNA双链断裂（DSB）情况，并观察7天内的细胞增殖。对球体在14天内监测其增殖情况并测量球体体积。
在DTX和GNP处理的单层样品中，与DTX相比，5戈瑞和10戈瑞照射后的存活率降低了16 - 24%，DSB增加了91.6 - 109.9%。在球体中，与对照相比，GNP使存活细胞减少了10.54 - 15.61%，而GNP和DTX联合使存活率降低了20.9 - 31.04%。三联组合处理14天后球体体积减小。
GNP与DTX联合在球体中产生协同放射增敏作用，该球体模型能更好地模拟肿瘤微环境。用球体和放疗测试治疗方式可能会使更快地转化到临床成为可能。
在线版本包含可在10.1186/s12645 - 023 - 00231 - 5获取的补充材料。
