Evaluation of Radiosensitization and Cytokine Modulation by Differentially PEGylated Gold Nanoparticles in Glioblastoma Cells.
Fiche publication
Date publication
juin 2023
Journal
International journal of molecular sciences
Auteurs
Membres identifiés du Cancéropôle Est :
Pr ROUX Stéphane
Tous les auteurs :
Kerr BN, Duffy D, McInerney CE, Hutchinson A, Dabaja I, Bazzi R, Roux S, Prise KM, Butterworth KT
Lien Pubmed
Résumé
Glioblastoma (GBM) is known as the most aggressive type of malignant brain tumour, with an extremely poor prognosis of approximately 12 months following standard-of-care treatment with surgical resection, radiotherapy (RT), and temozolomide treatment. Novel RT-drug combinations are urgently needed to improve patient outcomes. Gold nanoparticles (GNPs) have demonstrated significant preclinical potential as radiosensitizers due to their unique physicochemical properties and their ability to pass the blood-brain barrier. The modification of GNP surface coatings with poly(ethylene) glycol (PEG) confers several therapeutic advantages including immune avoidance and improved cellular localisation. This study aimed to characterise both the radiosensitizing and immunomodulatory properties of differentially PEGylated GNPs in GBM cells in vitro. Two GBM cell lines were used, U-87 MG and U-251 MG. The radiobiological response was evaluated by clonogenic assay, immunofluorescent staining of 53BP1 foci, and flow cytometry. Changes in the cytokine expression levels were quantified by cytokine arrays. PEGylation improved the radiobiological efficacy, with double-strand break induction being identified as an underlying mechanism. PEGylated GNPs also caused the greatest boost in RT immunogenicity, with radiosensitization correlating with a greater upregulation of inflammatory cytokines. These findings demonstrate the radiosensitizing and immunostimulatory potential of ID11 and ID12 as candidates for RT-drug combination in future GBM preclinical investigations.
Mots clés
cytokines, glioblastoma, gold nanoparticles, radiation, radiobiology, radiotherapy
Référence
Int J Mol Sci. 2023 06 12;24(12):