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Title: Investigating self-assembling nanomaterials (Sans) within a biological environment
Author: Dichello, Gennaro
ISNI:       0000 0004 7427 0775
Awarding Body: University of Brighton
Current Institution: University of Brighton
Date of Award: 2017
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Nanomaterials are defined as structures possessing one or more dimensions below 100 nanometres in size. They display unique properties that arise as a result of quantum behaviours, owing to their high surface area to volume ratios. Self-assembling nanomaterials (SANs), where individual components referred to as “building blocks” spontaneously organise into complex structural arrangements, is a prominent field that offers technological innovation within medicine and beyond. To effectively exploit this approach in healthcare however, a high-level of behavioural understanding within biological systems is required, which has yet to be ascertained. Accordingly, work undertaken in this thesis aimed to investigate how gold nanoparticles self-assemble and interact within a biological environment. Molecular recognition and electrostatic attraction, two different underpinning mechanisms of self-assembly were studied. Based on findings within this thesis, the latter approach was chosen for further development. Corresponding functional gold nanoparticles were incorporated into PEGylated liposomes using a novel method and extensively characterised. Comparative cytotoxicity evaluation was carried out in vitro on a male Chinese hamster lung fibroblast cell line (V79), employing MTT and LDH assays. Investigations focused on identifying any differences in biological response after treatment with individually dispersed gold nanoparticles and as they underwent in situ self-assembly. Cellular uptake and any ensuing self-assembly was investigated using a combination of electron microscopy and elemental analysis on thin-sectioned specimens. Results presented in this thesis reveal that both electrostatic interactions and molecular recognition facilitate self-assembly under aqueous conditions. Within a biologically relevant medium however, considerable nanoparticlebiomolecule complex formation occurs and only particles exploiting electrostatic interactions persist to self-assemble. Gold nanoparticles were capable of being encapsulated within liposomes by exploiting electrostatic attractions between oppositely charged lipids and ligands on particle surfaces. The novel method resulted in variable internalised gold to lipid ratios, hypothesised to result from differing magnitudes of electrostatic attraction during preparation. At clinically relevant concentrations, gold nanoparticles functionalised with cationic or anionic ligands did not display significant cytotoxicity. A significant difference in cytotoxicity was displayed as they underwent in situ assembly however. Cellular internalisation of gold was evidenced, with nanoparticles seen to accumulate and reside within cellular vacuoles, but no confirmation of self-assembly was obtained. In conclusion, the current work provides further knowledge regarding the feasibility, risk and current limitations associated with utilising and evaluating nanomaterials for in-situ self-assembly within biological environments. Extensive interactions shown to occur between initial building blocks and biological components can hinder self-assembly activity, highlighting the importance of rational design when manufacturing SANs. Individual nanoparticles were encapsulated within surface-modified liposomes, demonstrating a possible strategy towards implementing further control over SANs. Cellular studies identified a difference in toxicity between individual building blocks and their assembled suprastructures, demonstrating that unique biological responses could arise from the self-assembly of SANs. Evaluation of intracellular self-assembly and the ability to differentiate between individual building blocks, assembled suprastructures and cellular components is inherently difficult. Current techniques and approaches require further development to enable routine and reliable assessment of analogous in situ self-assembling nanosystems.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available