Enhancing nanoparticle accumulation in two dimensional, three dimensional, and xenograft mouse cancer cell models in the presence of docetaxel
Kyle Bromma, Nancy Dos Santos, Ingrid Barta, Abraham Alexander, Wayne Beckham, Sunil Krishnan, Devika B. Chithrani
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.