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

Abstract

BackgroundMuch 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.MethodsTwo 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 mathrm{mu g}/mathrm{mL} 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.ResultsIn 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.ConclusionsCombining 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.