Enhancing nanoparticle accumulation in two dimensional, three dimensional, and xenograft mouse cancer cell models in the presence of docetaxel
Date
2022
Authors
Bromma, Kyle
Dos Santos, Nancy
Barta, Ingrid
Alexander, Abraham S.
Beckham, Wayne
Krishnan, Sunil
Chithrani, Devika B.
Journal Title
Journal ISSN
Volume Title
Publisher
Scientific Reports
Abstract
Recent clinical trials show docetaxel (DTX), given in conjunction with radiation therapy (RT) and
androgen suppression, improves survival in high-risk prostate cancer. Addition of gold nanoparticles
(GNPs) to this current DTX/RT protocol is expected to further improve therapeutic benefits
remarkably. However, the foundation for the triple combination of RT, DTX, and GNPs must be
elucidated to ensure quicker facilitation to the clinic. In this study, we explored the use of low
concentrations of DTX combined with GNPs in two prostate cancer cell lines in a two-dimensional
monolayer, a three-dimensional spheroid, and a mouse xenograft model. When used together, DTX
and GNPs induced a nearly identical relative increase in uptake of gold in both the spheroid model and
the mouse xenograft, which saw a 130% and 126% increase respectively after 24 h, showcasing the
benefit of using spheroids as an in vitro model to better optimize in vivo experiments. Further, the
benefits of using low concentrations of DTX combined with GNPs extended for over 72 h, allowing for
less frequency in dosing when translating to the clinic. Overall, these results highlight the benefits of
using DTX combined with GNPs and lays the groundwork for the translation of the triple combination
of RT, GNPs, and DTX to the clinic.
Description
Keywords
Centre for Advanced Materials and Related Technology (CAMTEC)
Citation
Bromma, K., Dos Santos, N., Barta, I., Alexander, A., Beckham, W., Krishnan, S., & Chithrani, D. B. (2022). “Enhancing nanoparticle accumulation in two dimensional, three dimensional, and xenograft mouse cancer cell models in the presence of docetaxel.” Scientific Reports, 12(13508). https://doi.org/10.1038/s41598-022-17752-5