Gold Nanomaterial–Biomolecule Interactions: Influence of Size, Gold Nanomaterial–Biomolecule Interactions: Influence of Size, Surface Chemistry, and Environment Surface Chemistry, and Environment

Gold nanomaterials have emerged as great candidates for biomedical applications because of their physicochemical properties and high biocompatibility. However, their performance strongly depends on their interactions with biomolecules and their stability under physiological environments. This dissertation investigates the effect of nanoparticle size, ligand chemistry, proteins, and storage time on the behavior of gold nanoparticles (AuNPs) in biologically relevant settings. Citrate-coated spherical AuNPs ranging from 5 to 60 nm were purchased and studied across three complementary projects. First, time-of-flight secondary ion mass spectrometry (ToF-SIMS) was employed to explain size/ligand- dependent L-cysteine (Cys) adsorption on AuNPs. Cyclic voltammetry was also employed to investigate their electrochemical reactivity. Both techniques revealed enhanced interaction with Cys for smaller nanoparticles driven by increased surface energies. Second, the impact of pH on Cys–AuNP interactions was assessed, showing that mildly acidic conditions can suppress Cys binding, which is greatest between pH 3 and 5 due to the chemical form of Cys. Finally, dynamic light scattering and X-ray absorption spectroscopy were used to characterize the aggregation behavior of the AuNPs of varying sizes and as a function of the presence of bovine serum albumin (BSA). Results indicated that the nanoparticle size strongly affected the extent of aggregation and colloidal stability, with smaller particles having a higher tendency to aggregate, but this effect was reversed in the presence of BSA because of steric repulsion between BSA-coated nanoparticles. Further, circular dichroism and ToF-SIMS indicated that BSA largely retained its secondary structure upon adsorption on the AuNPs. Collectively, these findings advance the mechanistic understanding of how nanomaterials' dimensions, surface chemistry, proteins, and storage time dictate their interactions with proteins and amino acids. The insights gained contribute to the rational design of gold-based nanomaterials with improved stability and biocompatibility, facilitating their potential use in targeted drug delivery, diagnostic imaging, and cancer therapeutics.

Name thesis:degree_name

Ph D

Discipline thesis:degree_discipline

Chemistry

Grantor dc:publisher

The University of Western Ontario

Year dc:date.issued

2025

Author dc:creator

• Kalantarian, Seyedeh Marzieh

Advisor dc:contributor.advisor

• Hedberg, Yolanda

• Protein corona
• Cyclic voltammetry
• Dynamic light scattering
• Time-of-flight secondary ion mass spectrometry
• Colloidal stability
• Aggregation

Statement dc:rights

• Attribution-NonCommercial-NoDerivatives 4.0 International

Language dc:language.iso

en

Handle dc:identifier.uri

https://hdl.handle.net/20.500.14721/38939

OAI identifier oai:identifier

oai:uwo.scholaris.ca:20.500.14721/38939