Irradiation Effects on Polymer-Grafted Gold Nanoparticles for Cancer Therapy

Marine Le Goas 1 Aurélie Paquirissamy 2 Dorra Gargouri 1 Giulia Fadda 3 Fabienne Testard 2 Caroline Aymes-Chodur 4 Emile Jubeli 4 Thierry Pourcher 5 Béatrice Cambien 6 Serge Palacin 1 Jean-Philippe Renault 2 Géraldine Carrot 1
1 LICSEN - Laboratoire Innovation en Chimie des Surfaces et NanoSciences
NIMBE UMR 3685 - Nanosciences et Innovation pour les Matériaux, la Biomédecine et l'Energie (ex SIS2M)
2 LIONS - Laboratoire Interdisciplinaire sur l'Organisation Nanométrique et Supramoléculaire
NIMBE UMR 3685 - Nanosciences et Innovation pour les Matériaux, la Biomédecine et l'Energie (ex SIS2M)
5 TIRO - UMR E4320 - Transporteurs en Imagerie et Radiothérapie en Oncologie
CEA - Commissariat à l'énergie atomique et aux énergies alternatives : DRF/BIAM, CNRS - Centre National de la Recherche Scientifique, TIRO-MATOs - UMR E4320 : UMR E4320
Abstract : In the context of cancer treatment, gold nanoparticles (AuNPs) are considered as very promising radiosensitizers. Here, well-defined polymer-grafted AuNPs were synthesized and studied under gamma irradiation to better understand the involved radiosensitizing mechanisms. First, various water-soluble and well-defined thiol-functionalized homopolymers and copolymers were obtained through Atom Transfer Radical Polymerization. They were then used as ligands in the one-step synthesis of AuNPs, resulting in stable hybrid metal-polymer nanoparticles. Second, these nano-objects were irradiated in solution by gamma rays at different doses. Structures were fully characterized through SEC, SAXS and SANS measurements, prior and after irradiation. We were thus able to quantify and to localize radiation impacts onto the grafted polymers, revealing the production sites of reactive species around AuNPs. Both external and near-surface scissions were observed. Interestingly, the ratio between these two effects was found to vary according to the nature of polymer ligands. Medium-range and long-distance dose enhancements could not be identified from the calculated scission yields, but several mechanisms were considered to explain high yields found for near-surface scissions. Then, cytotoxicity was shown to be equivalent for both non-irradiated and irradiated polymer-grafted NPs, suggesting that released polymer fragments were non-toxic. Finally, the potential to add bioactive molecules such as anticancer drugs has been explored by grafting doxorubicin (DOX) onto the polymer corona. This may lead to nano-objects combining both radiosensitization and chemotherapy effects. This work is the first one to study in details the impact of radiation on radiosensitizing nano-objects combining physical, chemical and biological analyses.
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Marine Le Goas, Aurélie Paquirissamy, Dorra Gargouri, Giulia Fadda, Fabienne Testard, et al.. Irradiation Effects on Polymer-Grafted Gold Nanoparticles for Cancer Therapy. ACS Applied Bio Materials, 2018, 2, pp.144-154. ⟨https://doi.org/10.1021/acsabm.8b00484⟩. ⟨10.1021/acsabm.8b00484⟩. ⟨cea-01951373⟩

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