Utilizing two-dimensional monolayer and three-dimensional spheroids to enhance radiotherapeutic potential by combining gold nanoparticles and docetaxel.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Supplementary Information: The online version contains supplementary material available at 10.1186/s12645-023-00231-5.