Functionalized Gold Nanoparticles for Cellular Uptake

Abstract

Nanoparticles attract vast international research interest for medical applications due to their ability to be manipulated via the incorporation of various ligands and ligands. These ligands enable the regulation of a diverse range of biomedical processes which take place at a nanometer scale. Two approaches are commonly used to co-functionalize AuNPs, these methods include synthesizing either a mixed monolayer or by using a bifunctional Polyethylene glycol (PEG) linker. This Thesis directly compares the two approaches by incorporating the use of an internalization and endosomal escape peptide to compare the two arrangements for stability, cell viability, internalization and radio sensitization. An extensive research effort employed to confirm peptide arrangement has revealed that difficulties arise due to the higher binding affinity of thiolated ligands to gold in comparison to amine terminated ligands which are commonly used to synthesize a linker surface arrangement. It is shown that the successful synthesis using a bifunctional linker is heavily dependent on the method of attachment coupled with the solvents used. Inductively coupled plasma mass spectrometry (ICP-MS) has indicated a statistical difference for internalization, demonstrating that the linker has elicited a higher internalization response for both cell lines with an overall F value of 181.8 and a P value of 0.0095 (P < 0.05 statistically significant) for the DU145 cell lines resulting in over 3 times the amount of gold within the cells. Stability studies and cell viability studies have also indicated enhanced stability for the linker samples and preliminary data obtained from a clonogenic survival assay has indicated enhanced radiosensitivity, with an SER 1.36 for the linker, which represents a 36% increase in radiosensitivity for the samples in comparison to the untreated control. Concurrent attachment studies have identified that cysteine binding efficiency can be optimized by altering the pH of an AuNP suspension to ̴ 8, while extensive collaboration efforts have established that the solvents used to attach the peptide and/or ligands is paramount to a successful, stable covalent attachment, and an essential criteria for successful synthesis using a linker using a pre-synthesized NHS ester.

Date of Award	Apr 2018
Original language	English
Sponsors	Department for Employment and Learning
Supervisor	Dorian Dixon (Supervisor) & George Burke (Supervisor)