Antibody-functionalized Gold Nanoparticles As tumor-targeting Radiosensitizers for Proton Therapy

• DOI: 10.2217/nnm-2018-0161
• Publication Date: 2019-01-24T11:18:12Z
• Authors: Sha Li; Sandra Bouchy; Sebastien Penninckx; Riccardo Marega; Ornella Fichera; Bernard Gallez; Olivier Feron; Philippe Martinive; Anne-Catherine He...; Carine Michiels; Stéphane Lucas
• Keywords: 0301 basic medicine; Radiation-Sensitizing Agents; EGFR; Cetuximab; Metal Nanoparticles; Electron; Antibodies; Cell Line; Proton Therapy/methods; 03 medical and health sciences; Microscopy, Electron, Transmission; Cell Line, Tumor; Proton Therapy; Transmission; Humans; protontherapy; Microscopy; Tumor; Cetuximab/chemistry; Radiation-Sensitizing Agents/chemistry; Metal Nanoparticles/chemistry; nanoparticle uptake; Gold/chemistry; gold nanoparticles; Gold; Antibodies/chemistry; radiosentizing effects

This study aimed at developing antibody-functionalized gold nanoparticles (AuNPs) to selectively target cancer cells and probing their potential radiosensitizing effects under proton irradiation.AuNPs were conjugated with cetuximab (Ctxb-AuNPs). Ctxb-AuNP uptake was evaluated by transmission electron microscopy and atomic absorption spectroscopy. Radioenhancing effect was assessed using conventional clonogenic assay.Ctxb-AuNPs specifically bound to and accumulated in EGFR-overexpressing A431 cells, compared with EGFR-negative MDA-MB-453 cells. Ctxb-AuNPs enhanced the effect of proton irradiation in A431 cells but not in MDA-MB-453 cells. These data indicate, for the first time, that combining enhanced uptake by specific targeting and radioenhancing effect, using conjugated AuNPs, is a promising strategy to increase cell killing by protontherapy.