Uptake and excretion dynamics of gold nanoparticles in cancer cells and fibroblasts

Abstract

Radiotherapy is one of the main treatments used to fight cancer. A major limitation of this modality is the lack of selectivity between cancerous and healthy tissues. One of the most promising strategies proposed in this last decade is the addition of nanoparticles with high-atomic number to enhance radiation effects in tumors. Gold nanoparticles (AuNPs) are considered as one of the best candidates because of their high radioenhancing property, simple synthesis and low toxicity. Ultra small AuNPs (core size of 2.4 nm and hydrodynamic diameter of 4.5 nm) covered with dithiolated diethylenetriaminepentaacetic acid (Au@DTDTPA) are of high interest because of their properties to bind MRI active or PET active compounds at their surface, to concentrate in some tumors and be eliminated via renal clearance thanks to their small size. These key figures make Au@DTDTPA the best candidate to develop image-guided radiotherapy. Surprisingly the capacity of the nanoparticles to penetrate cells, an important issue to predict radioenhancement, has not been established yet. Here, we report the uptake dynamics, internalization routes and excretion dynamics of Au@DTDTPA nanoparticles in various cancer cell lines including glioblastoma (U87-MG), chordoma (UM-Chor1), cervix (HeLa), prostate (PC3), and pancreatic (BxPC-3) cell lines as well as fibroblasts (Dermal fibroblasts). This study demonstrates a strong cell line dependence of the nanoparticle uptake and excretion dynamics. Different pathways of cell internalization evidenced here explain this dependence. As a major finding, the retention of Au@DTDTPA nanoparticles was found to be higher in cancer cells than in fibroblasts. This result strengthens the strategy of using nanoagents to improve tumor selectivity of radiation treatments. In particular Au@DTDTPA nanoparticles are good candidates to improve the treatment of radioresitant gliobastoma, pancreatic and prostate cancer in particular. In conclusion, the variability of cell-to-nanoparticle interaction is a new parameter to consider in the choice of nanoagents in a combined treatment.

Y2O3 Nanoparticles and X-ray Radiation-Induced Effects in Melanoma Cells

“…Compound solubility generally corresponds to a pH decrease and then it becomes difficult to identify the various roles of NPs and resulted solution [ 49 ]. On the other hand, different cell lines exhibit totally different behavior when exposed to the same NPs stimuli [ 50 ] while, in the same time, the uptake of NPs is cell dependent [ 51 ]. ROS was measured in many sensitization studies, without offering a complete understanding of the NPs effects with respect to chemical processes and biochemistry.…”

Mechanisms of nanoparticle radiosensitization

“…Cell traits are highly variable (Nicol et al, 2018). Nanoparticle uptake is cell dependant (Ivošev et al, 2020) and even localize differently between cell lines (X. Cai et al, 2011;Chen et al, 2011).…”

“…Cell traits are highly variable (Nicol et al, 2018). Nanoparticle uptake is cell dependant (Ivošev et al, 2020) and even localize differently between cell lines (X. Cai et al, 2011; Chen et al, 2011). Even when the mean uptake is statistically comparable, the heterogeneity between cells can be statistically different (Turnbull, Thierry, & Kempson, 2019).…”

Gold nanoparticles carrying or not anti-VEGF antibody do not change glioblastoma multiforme tumor progression in mice

“…The uptake rate varied though depending on the cell type [42]. In the same way, dithiolated diethylenetriaminepentaacetic acid ultrasmall nanoparticles (4.5 nm in size) showed strong cell line dependence of the nanoparticle uptake, being higher in the glioblastoma U87-MG, pancreatic BxPC-3 and prostate PC-3 than in other cell lines [43]. Then, if an intracellular target is intended for a particular tumor cell, the gold nanoparticle covering must be carefully chosen.…”