Three-dimensional Tumor Spheroids as a Tool for Reliable Investigation of Combined Gold Nanoparticle and Docetaxel Treatment
Date
2021
Authors
Bromma, Kyle
Alhussan, Abdulaziz
Perez, Monica Mesa
Howard, Perry
Beckham, Wayne
Chithrani, Devika B.
Journal Title
Journal ISSN
Volume Title
Publisher
Cancers
Abstract
Radiotherapy and chemotherapy are the gold standard for treating patients with cancer
in the clinic but, despite modern advances, are limited by normal tissue toxicity. The use of nanomaterials,
such as gold nanoparticles (GNPs), to improve radiosensitivity and act as drug delivery
systems can mitigate toxicity while increasing deposited tumor dose. To expedite a quicker clinical
translation, three-dimensional (3D) tumor spheroid models that can better approximate the tumor
environment compared to a two-dimensional (2D) monolayer model have been used. We tested the
uptake of 15 nm GNPs and 50 nm GNPs on a monolayer and on spheroids of two cancer cell lines,
CAL-27 and HeLa, to evaluate the differences between a 2D and 3D model in similar conditions.
The anticancer drug docetaxel (DTX) which can act as a radiosensitizer, was also utilized, informing
future potential of GNP-mediated combined therapeutics. In the 2D monolayer model, the addition
of DTX induced a small, non-significant increase of uptake of GNPs of between 13% and 24%, while
in the 3D spheroid model, DTX increased uptake by between 47% and 186%, with CAL-27 having a
much larger increase relative to HeLa. Further, the depth of penetration of 15 nm GNPs over 50 nm
GNPs increased by 33% for CAL-27 spheroids and 17% for HeLa spheroids. These results highlight
the necessity to optimize GNP treatment conditions in a more realistic tumor-life environment. A
3D spheroid model can capture important details, such as different packing densities from different
cancer cell lines, which are absent from a simple 2D monolayer model.
Description
Keywords
gold nanoparticles, multicellular spheroids, monolayer, docetaxel, uptake, cell nanomedicine
Citation
Bromma, K., Alhussan, A., Mesa Perez, M., Howard, P., Beckham, W., & Chithrani, D. B. (2021). Three-Dimensional Tumor Spheroids as a Tool for Reliable Investigation of Combined Gold Nanoparticle and Docetaxel Treatment. Cancers, 13(6), 1-19. https://doi.org/10.3390/cancers13061465.