Synthesis, Functionalisation, and Biomedical Application of Phospholipid-Functionalised Gold Nanorods for Cancer Therapy

Cancer is the most common cause of death in the UK. Due to its aging population, the rate of cancer diagnoses is expected to rise dramatically in the coming decades. Currently cancer treatments have harsh side effects that cannot be well tolerated by the elderly, hence there is a need to develop new methods of cancer therapy which offer substantially better patient experiences. One such route is the use of near infrared--absorbent gold nanorods (AuNRs), which offer suitable optical and thermal properties to enable their use in techniques such as photothermal therapy and photoacoustic imaging. In this thesis we will explore the use of AuNRs in these roles as agents in cancer therapy. This is addressed in three core areas; firstly the seedless production of AuNRs using binary surfactants. It is demonstrated how the morphology and optical properties of such particles can be manipulated through the inclusion of a co-surfactant. As well as yielding improvements in the monodispersity, shape yield and scalability of the protocol. Secondly, the surface functionalisation of AuNRs with phospholipids, we demonstrate the effective removal of CTAB, a toxic surfactant used in the synthesis, this is demonstrated through the use of 1H nuclear magnetic spectroscopy, surface enhanced Raman spectroscopy and pH-dependent zeta potential measurements, this is present alongside stability studies of AuNRs of different coating, demonstrating the improved stability of AuNRs prepared with phospholipids. Finally, the application of phospholipid-coated AuNRs in cancer therapy is explored. We show that these particles are non--toxic in vitro and in vivo. We also explore their efficacy as photothermal conversion agents, measuring the achievable temperature rises under CW illumination, as well as imaging them using multispectral optoacoustic tomography of the particles in phantoms. In vivo measurements of the effects of heating these AuNRs under CW and nanosecond lasers on human carcinoma cell lines were also investigated. Finally the biodistribution of these particles was explored, when passively targeted or functionalised with cancer specific adhirons though ICP-MS analysis of ex vivo murine samples

Exploring High Aspect Ratio Gold Nanotubes as Cytosolic Agents: Structural Engineering and Uptake into Mesothelioma Cells.

The generation of effective and safe nanoagents for biological applications requires their physicochemical characteristics to be tunable, and their cellular interactions to be well characterized. Here, the controlled synthesis is developed for preparing high-aspect ratio gold nanotubes (AuNTs) with tailorable wall thickness, microstructure, composition, and optical characteristics. The modulation of optical properties generates AuNTs with strong near infrared absorption. Surface modification enhances dispersibility of AuNTs in aqueous media and results in low cytotoxicity. The uptake and trafficking of these AuNTs by primary mesothelioma cells demonstrate their accumulation in a perinuclear distribution where they are confined initially in membrane-bound vesicles from which they ultimately escape to the cytosol. This represents the first study of the cellular interactions of high-aspect ratio 1D metal nanomaterials and will facilitate the rational design of plasmonic nanoconstructs as cytosolic nanoagents for potential diagnosis and therapeutic applications.BLF-Papworth Fellowship from the British Lung Foundation and the Victor Dahdaleh Foundation

Sub‐nanometer thick gold nanosheets as highly efficient catalysts

2D metal nanomaterials offer exciting prospects in terms of their properties and functions. However, the ambient aqueous synthesis of atomically‐thin, 2D metallic nanomaterials represents a significant challenge. Herein, freestanding and atomically‐thin gold nanosheets with a thickness of only 0.47 nm (two atomic layers thick) are synthesized via a one‐step aqueous approach at 20 °C, using methyl orange as a confining agent. Owing to the high surface‐area‐to‐volume ratio, abundance of unsaturated atoms exposed on the surface and large interfacial areas arising from their ultrathin 2D nature, the as‐prepared Au nanosheets demonstrate excellent catalysis performance in the model reaction of 4‐nitrophenol reduction, and remarkable peroxidase‐mimicking activity, which enables a highly sensitive colorimetric sensing of H2O2 with a detection limit of 0.11 × 10−6 m. This work represents the first fabrication of freestanding 2D gold with a sub‐nanometer thickness, opens up an innovative pathway toward atomically‐thin metal nanomaterials that can serve as model systems for inspiring fundamental advances in materials science, and holds potential across a wide region of applications

Sub‐nanometer thick gold nanosheets: sub‐nanometer thick gold nanosheets as highly efficient catalysts (Adv. Sci. 21/2019)

In article number 1900911, Stephen D. Evans and co‐workers develop an ambient aqueous synthesis for preparing atomically‐thin gold nanosheets (termed gold nanoseaweed, AuNSW, because of its morphology, color and aqueous growth). These AuNSWs represent the first free‐standing 2D gold with a sub‐nanometer thickness (0.47 nm, e.g., two atomic layers thick), and exhibit excellent catalysis performance in the model reaction of 4‐nitrophenol reduction, as well as remarkable peroxidase‐mimicking activity

Sub‐nanometer thick gold nanosheets: sub‐nanometer thick gold nanosheets as highly efficient catalysts (Adv. Sci. 21/2019)

In article number 1900911, Stephen D. Evans and co‐workers develop an ambient aqueous synthesis for preparing atomically‐thin gold nanosheets (termed gold nanoseaweed, AuNSW, because of its morphology, color and aqueous growth). These AuNSWs represent the first free‐standing 2D gold with a sub‐nanometer thickness (0.47 nm, e.g., two atomic layers thick), and exhibit excellent catalysis performance in the model reaction of 4‐nitrophenol reduction, as well as remarkable peroxidase‐mimicking activity

Dataset associated with 'Morphological Control of Seedlessly--Synthesised Gold Nanorods using Binary Surfactants’

TEM, UV-Vis and darkfield data associated with synthesised samples. Paper URL: https://doi.org/10.1088/1361-6528/aaa99

Symmetric plasmonic nanoparticle clusters: Synthesis and novel optical properties

The strong resonant interaction of plasmonic particles with light has been used in a wide range of applications in recent years. The high sensitivity of the coupling between plasmon resonances to the interparticular distance between neighboring particles offers a powerful tool to tune their optical properties. More recently, the discovery that specific geometries of groupings of nanoparticles, or plasmonic nanoparticle clusters, can generate remarkable optical properties such as optical magnetism has motivated the development of new fabrication techniques. Such clusters could serve as building blocks in a new generation of self-assembled metamaterials. In this article, we describe the geometries, fabrication techniques and optical properties of symmetric clusters of plasmonic particles

Applications of machine learning in supercritical fluids research

Machine learning has seen increasing implementation as a predictive tool in the chemical and physical sciences in recent years. It offers a route to accelerate the process of scientific discovery through a computational data-driven approach. Whilst machine learning is well established in other fields, such as pharmaceutical research, it is still in its infancy in supercritical fluids research, but will likely accelerate dramatically in coming years. In this review, we present a basic introduction to machine learning and discuss its current uses by supercritical fluids researchers. In particular, we focus on the most common machine learning applications; including: (1) The estimation of the thermodynamic properties of supercritical fluids. (2) The estimation of solubilities, miscibilities, and extraction yields. (3) Chemical reaction optimization. (4) Materials synthesis optimization. (5) Supercritical power systems. (6) Fluid dynamics simulations of supercritical fluids. (7) Molecular simulation of supercritical fluids and (8) Geosequestration of CO2 using supercritical fluids

Bottom-up synthesis of meta-atoms as building blocks in self-assembled metamaterials: recent advances and perspectives

International audienceMeta-atoms interact with light in interesting ways and offer a large range of exciting properties. They exhibit optical properties inaccessible by natural atoms but their fabrication is notoriously difficult because of the precision required. In this perspective, we present the current research landscape in making meta-atoms, with a focus on the most promising self-assembly approaches and main challenges to overcome, for the development of materials with novel properties at optical frequencies

Controlling disorder in self-assembled colloidal monolayers via evaporative processes

International audienceMonolayers of assembled nano-objects with a controlled degree of disorder hold interest in many optical applications, including photovoltaics, light emission, sensing, and structural coloration. Controlled disorder can be achieved through either top-down or bottom-up approaches, but the latter is more suited to large-scale, low-cost fabrication. Disordered colloidal monolayers can be assembled through evaporatively driven convective assembly, a bottom-up process with a wide range of parameters impacting particle placement. Motivated by the photonic applications of such monolayers, in this review we discuss the quantification of monolayer disorder, and the assembly methods that have been used to produce them. We review the impact of particle and solvent properties, as well as the use of substrate patterning, to create the desired spatial distributions of particles