Mellor, Ryan David; (2023) Development of bio-functionalized, Raman responsive, excretable gold nanoclusters. Doctoral thesis (Ph.D), UCL (University College London).

Text Ryan Mellor - PhD Thesis.pdf - Accepted Version Access restricted to UCL open access staff until 1 December 2026. Download (11MB)

Abstract

Aims: Synthesis of biofunctionalized ultrasmall-in-nano gold constructs. The diameter of the constructs should be in the range of 100-200 nm resulting in strong absorbance in the phototherapeutic window. The constructs should by comprised of sub-5 nm gold nanoparticles (AuNPs) which can be liberated in vivo and excreted. Methods: Amphiphilic glycol chitosan derivative ‘GCPQ’ was synthesized by degradation, palmitoylation, and quaternization of the starting material, for certain experiments the polymer was further derivatized by thiolation. Ultrasmall-in-nano gold constructs were generated by clustering of sub-5 nm AuNPs. A method of active targeting, using the anti-EGFR aptamer MinE07, was validated in vivo by use of a paclitaxel conjugate and detection by LC-MS. Results: Sub-5 nm AuNPs were synthesized and reversibly clustered to ultrasmall-in-nano gold construct with the desired optical properties. Bio-distribution of aptamer conjugate showed preferential tumour accumulation compared to free paclitaxel, however the difference is not statistically significant and will need to be reproduced. Conclusions: Ultrasmall-in-nano constructs have been generated with the desired optical and structural properties. Keywords: Ultrasmall-in-Nano, Excretable, Gold, Clusters, Raman, Phototherapeutic

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