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Aim: This study aimed at developing antibody-functionalized gold nanoparticles (AuNPs) to selectively target cancer cells and probing their potential radiosensitizing effects under proton irradiation., Materials & Methods: 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., Results & Conclusion: 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.

Understanding the targeted cellular uptake of nanomaterials is an essential step to engineer and program functional and effective biomedical devices. In this respect, the targeting and ultrafast uptake of zeolite nanocrystals functionalized with Cetuximab antibodies (Ctxb) by cells overexpressing the epidermal growth factor receptor are described here. Biochemical assays show that the cellular uptake of the bioconjugate in the targeted cancer cells already begins 15 min after incubation, at a rate around tenfold faster than that observed in the negative control cells. These findings further show the role of Ctxb exposed at the surfaces of the zeolite nanocrystals in mediating the targeted and rapid cellular uptake. By using temperature and pharmacological inhibitors as modulators of the internalization pathways, the results univocally suggest a dissipative uptake mechanism of these nanomaterials, which seems to occur using different internalization pathways, according to the targeting properties of these nanocrystals. Owing to the ultrafast uptake process, harmless for the cell viability, these results further pave the way for the design of novel theranostic tools based on nanozeolites., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)