Relating gold nanostar shape to function: a study on the applicability of nanostars for photothermal therapy and cellular uptake
File(s)
Author(s)
Morton, William
Type
Thesis
Abstract
The following thesis presents a study on gold nanostars, focusing on their geometric properties, characterisation, and applications for photothermal therapy. In this application, the nanostar geometry is crucial for optimising optical properties, specifically the localised surface plasmon resonance and absorption cross-section, which can result in the particle heating when exposed to light. If the nanostar can enter a tumour, it could thermally ablate the cancerous region.
However, a fundamental challenge in nanostar characterisation is accurately estimating geometric properties such as particle volume, surface area, and the number of tips. The errors in estimation using Transmission Electron Microscopy (TEM) are first investigated through an analytical investigation, for which a library of 6000 nanostars was created. A statistical analysis suggests that current methods overestimate nanostar volumes, creating discrepancies across studies. A novel method is developed to address this shortcoming by combining Ultraviolet-visible spectroscopy (UV-Vis), TEM images, and Discrete Dipole Approximation (DDA) to characterise nanostar geometry more precisely. Once the geometry is predicted, the absorption cross-section can then be estimated using DDA.
Understanding the interaction between nanostars and cell membranes is crucial to understanding their potential use as therapeutics. A molecular dynamics method was reparametrized to better represent the binding limitations of ligands and receptors. Nanostar endocytosis was then studied, assuming cellular uptake is driven by these ligand receptor bonds. By controlling the distribution of nanostar tips the uptake speed can not only be tuned, but wholly inhibited by specific cell types, revolutionising the potential for targeted cell delivery.
In conclusion, this thesis offers a unifying method for estimating nanostar geometry, and suggests optimal geometric factors for cell targeting. While the benefits of gold nanostars as photothermal therapeutics are highlighted, I propose that the field instead capitalises on advancements in ligand and protein design for controlling cellular processes through nanoparticle surface interactions.
However, a fundamental challenge in nanostar characterisation is accurately estimating geometric properties such as particle volume, surface area, and the number of tips. The errors in estimation using Transmission Electron Microscopy (TEM) are first investigated through an analytical investigation, for which a library of 6000 nanostars was created. A statistical analysis suggests that current methods overestimate nanostar volumes, creating discrepancies across studies. A novel method is developed to address this shortcoming by combining Ultraviolet-visible spectroscopy (UV-Vis), TEM images, and Discrete Dipole Approximation (DDA) to characterise nanostar geometry more precisely. Once the geometry is predicted, the absorption cross-section can then be estimated using DDA.
Understanding the interaction between nanostars and cell membranes is crucial to understanding their potential use as therapeutics. A molecular dynamics method was reparametrized to better represent the binding limitations of ligands and receptors. Nanostar endocytosis was then studied, assuming cellular uptake is driven by these ligand receptor bonds. By controlling the distribution of nanostar tips the uptake speed can not only be tuned, but wholly inhibited by specific cell types, revolutionising the potential for targeted cell delivery.
In conclusion, this thesis offers a unifying method for estimating nanostar geometry, and suggests optimal geometric factors for cell targeting. While the benefits of gold nanostars as photothermal therapeutics are highlighted, I propose that the field instead capitalises on advancements in ligand and protein design for controlling cellular processes through nanoparticle surface interactions.
Version
Open Access
Date Issued
2023-07
Date Awarded
2024-02
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Angioletti-Uberti, Stefano
Xie, Fang
Sponsor
Department of Materials
Publisher Department
Materials
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)