Developing targeted photodynamic therapy using glyconanoparticles

Moore, Brydie (2019) Developing targeted photodynamic therapy using glyconanoparticles. Doctoral thesis, University of East Anglia.

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Abstract

Current antibiotics are losing efficacy due to the rapid rise and spread of drug resistant bacteria; and conventional cancer treatments can present many nasty side effects. Consequently, we urgently need to find alternative therapies to develop effective treatments and improve patient outcomes. One such approach is targeted photodynamic therapy (PDT), which uses a non-toxic dye (photosensitiser) that releases cytotoxic reactive oxygen species on activation with specific wavelengths of light. Here, glycan-modified 16 nm gold nanoparticles (glycoAuNPs) were explored for their use in targeted PDT, whereby the dye was localisedtothetargetcellthroughselectiveglycan-lectininteractions. Two novel glycan ligands were synthesised by Cu(I)-catalysed Huisgen azide-alkyne cycloaddition ‘click chemistry’, and used to modify AuNPs. By exploiting the unique colorimetric properties of AuNPs, detection of glycan-lectin interactions was possible. Target pathogen Pseudomonas aeruginosa lectin: LecA, wasdetectedat64nM,byUV-Visspectroscopy-basedstudies. Through a new filtration method that was developed in collaboration with Iceni Diagnostics, binding of different bacterial species was observed by the modified AuNPs. Finally, differential glycan binding by breast cancer and non-cancer cell lines was assessedtoidentifyaglycantoselectivelytargetoverexpressedglycan-binding proteins on breast cancer cells. AuNPs were modified with photosensitiser and glycan(glycan-/ce6-AuNPs),andtargetedcellkillingofbreastcancercellswas achieved,showingaca46%reductionincellviabilityuponlighttreatment. The findings demonstrate the versatility of using glycoAuNPs for selective binding to different cellular targets (bacterial and cancer cells), through glycanlectin interactions. The selective cell killing of breast cancer cells demonstrates the potential of using this approach for targeted PDT.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Science > School of Biological Sciences
Depositing User: Katherine Whittaker
Date Deposited: 14 Feb 2020 16:07
Last Modified: 14 Feb 2020 16:07
URI: https://ueaeprints.uea.ac.uk/id/eprint/74204
DOI:

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