Exploiting the ‘Complex’ Relationship between Cucurbit[7]uril, Peptides and Gold Nanoparticles for the Development of Biomaterials Suitable for Delivery
type: CreativeWork
description: This thesis explores aspects of cucurbit[n]uril (CB[n]) chemistry that can be utilised and exploited in the formation of materials suitable for therapeutic peptide delivery and diagnostics. Biomedical applications of CB[n] span simple therapeutic complexation leading to increased solubility and circulation times as well as their incorporation into more complex designs. CB[7] exhibits the strongest binding affinities of the CB[n] family as well as the highest water solubility, making it of high biomedical interest. Therefore, it is the homologue that is investigated throughout this thesis. Chapter 1 introduces the CB[n] family, taking the reader from synthetic functionalisation, an overview of CB[n] utility in biomedical applications such as peptide delivery and analyte detection, ending with a brief description of techniques used to characterise CB[n] complexes. In Chapter 2, isothermal titration calorimetry methodology is developed for the characterisation of ultra-tight CB[7]-guest binary complexes enabling accurate determination of complexes with affinities up to 10¹⁷ M⁻¹. This methodology is then used to assess the binding strength between CB[7] and immunogenic peptide, SIINFEKL, modified with a variety of binding motifs in Chapter 3. In vitro investigations into the effect of binding strength on the bio-activity of SIINFEKL peptides complexed with CB[7] is assessed. The ideal binding motif is dependent on the mechanism of therapeutic action. Functionalisation of CB[n] opens up avenues for its use in more complex architectures. Chapter 4 explores the functionalisation of CB[7] with short thiolated poly(ethylene) glycol (PEG) chains (CB[7]SH) and reports the facile route towards isolation of allyloxy CB[7] species with a definitive number of functional groups. Following these successful results, methodology was applies to CB[8] resulting in an allyloxy CB[8] species, yet to be reported in the literature. These preliminary results are reported in the Appendix. The…
abstract: This thesis explores aspects of cucurbit[n]uril (CB[n]) chemistry that can be utilised and exploited in the formation of materials suitable for therapeutic peptide delivery and diagnostics. Biomedical applications of CB[n] span simple therapeutic complexation leading to increased solubility and circulation times as well as their incorporation into more complex designs. CB[7] exhibits the strongest binding affinities of the CB[n] family as well as the highest water solubility, making it of high biomedical interest. Therefore, it is the homologue that is investigated throughout this thesis. Chapter 1 introduces the CB[n] family, taking the reader from synthetic functionalisation, an overview of CB[n] utility in biomedical applications such as peptide delivery and analyte detection, ending with a brief description of techniques used to characterise CB[n] complexes. In Chapter 2, isothermal titration calorimetry methodology is developed for the characterisation of ultra-tight CB[7]-guest binary complexes enabling accurate determination of complexes with affinities up to 10¹⁷ M⁻¹. This methodology is then used to assess the binding strength between CB[7] and immunogenic peptide, SIINFEKL, modified with a variety of binding motifs in Chapter 3. In vitro investigations into the effect of binding strength on the bio-activity of SIINFEKL peptides complexed with CB[7] is assessed. The ideal binding motif is dependent on the mechanism of therapeutic action. Functionalisation of CB[n] opens up avenues for its use in more complex architectures. Chapter 4 explores the functionalisation of CB[7] with short thiolated poly(ethylene) glycol (PEG) chains (CB[7]SH) and reports the facile route towards isolation of allyloxy CB[7] species with a definitive number of functional groups. Following these successful results, methodology was applies to CB[8] resulting in an allyloxy CB[8] species, yet to be reported in the literature. These preliminary results are reported in the Appendix. The…
author: King, Katherine
language: eng
keywords: nanoparticles, gold, peptides, delivery, biomaterials, ITC, binding, precision medicine, cucurbit[n]urils, self-assembly, SERS, therapeutic peptides, anti-cancer peptides, targeting, aggregates, disassembly
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2021-10-08
date modified: 2026-07-22T22:24:17Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.86477