Role of nanoparticle size and shape in the design and
characterisation of functional nanomaterials for
applications in cancer nanotechnology

Greenwood, M

Abstract

Gold nanoparticles are emerging novel theranostic agents with numerous applications as
diagnostic and therapeutic tools owing to their unique optical properties and highly
customisable surface chemistry, which allows for the careful design of personalised medicine
upon grafting with therapeutic agents of interest. The stability and therapeutic action of
functionalised nanomaterials in biological systems is at times challenged by undesired
interactions with biomolecules, and is strongly dependent on their physico-chemical
properties, which require a complex and detailed approach to the design of analytical
methods and drug analysis, often using diverse analytical strategies that are usually not
required for the analysis of approved small molecule drugs. Accurate in situ quantification
methods for drug loading allows suitable comparisons to be made with the free drug for in
vitro and in vivo therapeutic profiling of functional gold nanoparticles.
This thesis focuses on the design, synthesis, and characterisation of cisplatin and doxorubicin
conjugated gold nanoparticles, and represents a systematic study on the role of particle size
and shape on in vitro cell viability against A549 lung cancer cells, BEAS-2B immortalised
lung epithelial cells, and MB03 adolescent medulloblastoma cells. Comprehensive
characterisation at each stage of functional-nanoparticle design is described in detail,
featuring key characterisation steps including analysis of the particle distributions in
biological media, determination of drug loading, and theoretical estimates of drug orientation
and particle number concentration. Inductively coupled plasma-optical emission spectroscopy
(ICP-OES) was used in this work for the first time to demonstrate quantitative analysis of
aquated-cisplatin loaded gold nanoparticles and validated in a comparative study of the
atomic gold content analysis using UV-visible spectroscopy. A novel simplified strategy that
aims to estimate the length of functional ligands grafted on the surface of gold nanoparticles
using differential centrifugal sedimentation (DCS) analysis was also explored, which can be
applied to the description of systems with compromised stability in situ in biological media.
Like gold nanoparticles, those constructed from copper present a number of unique properties
that may be exploited, through considered design, in a variety of applications. Copper
nanoparticles are of active interest in the fields of catalysis and microbiology, and may in
future provide a more cost effective alternative to, or base structure in the production of,
more noble metal particles. A novel green synthesis method for the fabrication of controllably
shaped copper nanostructures around 200 nm in diameter was developed by variation of
reaction parameters, chiefly pH and air exposure, and preliminary antimicrobial studies
against S. aureus and E. faecalis reported.
This thesis represents a collection of chapters designed with the aim to address a systematic
study of the role of particle size and shape on biological responses, with regards to both
anticancer and antimicrobial activity, and validates the effects of functionalised nanoparticles
for their use as novel anticancer therapeutics, outlining the key steps to comprehensive
analysis of drug-nanoparticle drug delivery vehicles.

Citation

applications in cancer nanotechnology. (Thesis). University of Salford

• Thesis Type: Thesis
• Deposit Date: Apr 12, 2023
• Award Date: Sep 30, 2022