Novel Multivalent Glyco-Nanomaterials as Potential Theranostics

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)

Abstract

Cell surface carbohydrates play a key role in cell-cell recognition, this occurs via lectin proteins from one cell interacting with terminal sugar molecules on another. These interactions are ubiquitous throughout life with roles ranging from fertilisationto bacterial invasion. However, the downstream effects of carbohydrate interactions are not fully understood, partly due to the difficulty in isolating interactions for study. Using well characterised non-toxic carbon dots (CDs) we developed probes towards theidentification of cell surface carbohydrate profiles and to assess the multivalent lectin binding strength via Förster resonance energy transfer (FRET) between two non-toxic, fluorescent probes in solution.We developed an assay and probed the specific interaction of Concanavalin A (ConA) lectin in this system.

Secondly, we explored the anti-cancer therapeutic potential of these glyco-carbon dots for improved chemotherapy drug –doxorubicin, delivery. Exploiting the enhanced permeabilityand retention (ERP) effect exhibited with nanoparticles for enhanced delivery as well as carbohydrate functionalisation for targeted delivery. We observe anti-cancer potential in this work and uncover a slow release mechanism for the delivery of doxorubicin to the site of action.

Finally, we assessed the photothermal therapy (PTT) potential of a novel carbon dot for anti-cancer treatment observing both cancer cell targeting and cytotoxicity. This work contributes to the development of non-invasive localised cancer treatments which involve a nanoparticle and external trigger component. This is important for the development of improved cancer therapies.
Date of Award29 Sep 2020
Original languageEnglish
Awarding Institution
  • The University of Bristol
SupervisorHenkjan Gersen (Supervisor) & M C Galan (Supervisor)

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