Sola Barrado, María Belén;
(2021)
Combinatorial Intracellular Delivery Screening of Anticancer Drugs.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Conventional drug solubilisation strategies limit the understanding of the full potential of poorly water-soluble drugs during drug screening. Here, I propose a screening approach in which poorly water-soluble drugs are entrapped in poly (2- (methacryloyloxyethyl phosphorylcholine)-poly(2-(diisopropylaminoethyl methacryate) (PMPC-PDPA) or Angiopep-2-poly(ethylene glycol)-PDPA (AP-PEG-PDPA) polymersomes (POs) to enhance drug solubility and facilitate intracellular delivery. By using a human paediatric glioma cell model, I demonstrated that PMPC-PDPA and AP-PEG-PDPA POs mediated intracellular delivery of cytotoxic and epigenetic drugs by receptor-mediate endocytosis. Additionally, when delivered in combination, drug-loaded PMPC-PDPA and AP-PEG-PDPA POs triggered both an enhanced drug efficacy and synergy compared to that of a conventional combinatorial screening. Hence, our comprehensive synergy analysis illustrates that our screening methodology, in which PMPC-PDPA and AP-PEG-PDPA POs are used for intracellular co-delivery of drugs, allows us to identify potent synergistic profiles of anticancer drugs.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Combinatorial Intracellular Delivery Screening of Anticancer Drugs |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2022. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10140981 |
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