Gold nanoparticles (AuNP) are one of the most remarkable nanomaterials. They have aroused great interest in the last years due to their high potential for biomedical applications. Due to their small size, these nanoparticles can cross the blood-brain barrier, which makes them good candidates for the treatment of diseases related to the central nervous system. For all these applications, it is essential to discard any potential harmful effects. On this basis, the main objective of the present work was to evaluate the influence of surface charge on biological behaviour of AuNP by assessing the cytotoxic and genotoxic effects induced in neuronal cells exposed to AuNP with different charge, i.e. cationic, anionic and neutral. For this purpose, SH-SY5Y cells were treated with a range of concentrations of each type of nanoparticle for 3 and 24h. Cytotoxic effects were analysed by evaluating morphological alterations and changes in cell viability after AuNP exposure, whereas genotoxic effects were assessed by means of γH2AX assay, which detects DNA double strand breaks. Also, cellular uptake was evaluated by flow cytometry. The results obtained showed different toxicological behaviour depending on the surface charge of the nanoparticles. In particular, anionic and neutral AuNP did not cause cytotoxic effects, while cationic nanoparticles showed cytotoxicity. Furthermore, cationic and neutral AuNP showed a low genotoxic potential, while those with a negative charge did not induce double-strand breaks in DNA at all. The study of cellular uptake by flow cytometry did not provide conclusive results likely because the extremely small size of the AuNP hinders their detection.

Acknowledgments

This work was funded by Spanish Ministry of Science and Innovation: MCIN/AEI/10.13039/501100011033 (Grants PID2020-114908GA-I00 and PID2020-117856GA-I00), Xunta de Galicia (ED431B 2022/16), CICA-Disrupting Project 2021SEM-A1, and Ministry of Education, Culture and Sport [BEAGAL18/00142 to V.V.].