Thiolated metallic nanoparticles and their interactions with lipid membranes

Abstract

The thesis investigates the interactions between thiolated metal nanoparticles (electroactive and non-electroactive ligands), and complex thiolated polymeric gold nanoparticles with lipid membranes (artificial lipid models and biological bacterial cells) as a potential tool for drug carriers.
Nanoparticle (NP)-electrode collision behaviours of thiol-capped metal NPs on gold electrodes were investigated using Resonance Enhanced Surface Impedance (RESI) and Chronoamperometry (CA) in microfluidic cells setup with integrated electrodes. Factors such as flow rates and ligand electroactivity were found to have a significant impact on the NP-electrode collision events. The NP-electrode collision events of non-electroactive dodecanethiol (DDT) NPs were detected either as agglomerates or individual particles depending on their nano-impact sizing characteristics. While the introduction of electroactive ligands, ω-ferrocenylhexanethiolate (FcHT), generated NP-electrode collision events under potentiated electrode conditions (oxidising potential for ferrocene).
The investigation of the penetration behaviour of thiol-capped AuNPs (electroactive and non-electroactive) through artificial lipid membranes were undertaken using AFM, RESI and electrochemical techniques. The tBLM models were incubated in NPs solutions at different time intervals and the results revealed that NPs adsorption was the first stage of NPs-membrane interactions which was followed by lipid defects formation for the penetration of NPs through the lipid membrane, then lipid collapse and/or membrane displacement by NPs monolayer. The other investigation on the effect of NPs size (FcHT-AuNPs) on NPs-membrane interactions revealed that small NPs (5 nm) have non-destructive penetration behaviours, whereas larger NPs (10 and 20 nm) caused irreversible changes to the lipid membrane.
The investigation on the effect of NPs surface charge on NPs-membrane interactions with complex thiolated polymeric AuNPs revealed that the AuNPs containing bulky aromatic cationic ligands were not able to penetrate through tBLM models whilst aliphatic cationic ligands altered the membrane’s architecture as they penetrated through. MIC assay investigation using biological bacterial cells (E. coli) concluded that the presence of bulky aromatic substituents play a role in inhibiting bacterial growth.