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

Fiche publication

Date publication

novembre 2019

Journal

Nanotechnology

Auteurs

Membres identifiés du Cancéropôle Est :
Pr ROUX Stéphane

Tous les auteurs :
Ivosev V, Jimenez-Sanchez G, Porcel E, Yang X, González Vargas CR, Abi Haidar D, Bazzi R, Stefancikova L, Roux S, Lacombe S

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/31783387

Résumé

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 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 (AuNPs@DTDTPA) are of high interest because of their property 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 AuNPs@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 never been established yet. Here, we report the uptake dynamics, internalization routes and excretion dynamics of AuNPs@DTDTPA 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 AuNPs@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-Cy5 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.