Interaction of gold nanoparticles with neurons

Abstract

In the last few decades, advances in nanotechnology have resulted in the production and use of inorganic nanoparticles (NPs). These NPs have been used commercially for a range of applications, particularly in the biomedical field, based on their exceptional chemical and physical properties, which are very different to that in the larger scale. Our understanding regarding the NP interaction with the cells following NP exposure, prior to their use it is very important. This was the motivation for the work carried out in this thesis. Initially, the investigation presented in the thesis involved the synthesis of spherical and hollow gold NPs, which were then capped by water soluble organic oligo-ethylene glycol ligand (OEG). The OEG-capped NPs were then functionalised by attaching a specific cell targeting peptide, lysine terminated-Tet1, on their organic corona. The surface modification of the NPs by the aforementioned ligands, was carried out so that the NPs could be employed in the biological investigations carried out in this project. PC12 and SH-SY5Y cells, neuron-like cell lines, were exposed to the synthesised gold NPs, and the fate of these NPs within the cells was studied by using transmission electron microscopy (TEM). The TEM images revealed that spheres and hollow gold NPs were found within the PC12 cells, indicating that they were able to traverse through the cell membrane. Though, the pathway and cellular processes involved could not be specifically defined due to time constrains. Furthermore, the peptide-functionalised NPs targeted the GTb1 receptors which are readily expressed on PC12 and SH-SY5Y cells. Lysine terminated Tet1-functionalised NPs uptake seemed to be greater compared to OEG-capped NPs, and they were transported to the inner part of the cell around its perinuclear region. Nevertheless, further experiments involving fluorescently tagged NPs would give us an inside on the cellular events that take place following NP exposure, over time. In addition, western blot analysis of proteins involved in a cell stress response could give us information whether the cell is under a stress when it is exposed to gold NPs.
Furthermore, the application of the hyperspectral darkfield microscope designed by the Muskens group for imaging of single hollow gold NPs on a TEM grid and in a biological sample (with fixed SH-SY5Y cells), was also presented in this Thesis. The low illumination intensity used (<0:5 W/cm2) is a very good aspect of this setup for future studies with living cells and gold NPs. For example, single hollow gold NPs could be used as spectral sensors of a particular cell signalling pathway.

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Identifiers

ORCID for Antonios G. Kanaras: orcid.org/0000-0002-9847-6706

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