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

Cancer Nanotechnology

Research

Kyle Bromma¹  Wayne Beckham²  Devika B. Chithrani³ 

[1] Department of Physics and Astronomy, University of Victoria, Victoria, BC, Canada;Department of Physics and Astronomy, University of Victoria, Victoria, BC, Canada;British Columbia Cancer, Victoria, BC, Canada;Department of Physics and Astronomy, University of Victoria, Victoria, BC, Canada;British Columbia Cancer, Victoria, BC, Canada;Centre for Advanced Materials and Related Technologies (CAMTEC), University of Victoria, Victoria, BC, Canada;Division of Medical Sciences, University of Victoria, Victoria, BC, Canada;

关键词: Gold nanoparticles;    Docetaxel;    Radiotherapy;    Spheroids;    Cancer;    Nanomedicine;   

DOI  :  10.1186/s12645-023-00231-5

 received in 2023-06-27, accepted in 2023-10-08,  发布年份 2023

来源: Springer

【 摘 要 】

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 μg/mL\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$\mathrm{\mu g}/\mathrm{mL}$$\end{document} 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.

【 授权许可】

CC BY   
© Springer-Verlag GmbH Austria, part of Springer Nature 2023

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