Chaipanichkul, Premkamon;
(2025)
A nanoparticle uptake platform for characterisation of nanoparticle-enhanced radiotherapy.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Conventional radiotherapy often damages healthy tissue and may lead to secondary cancers, prompting the need for more targeted alternatives. Nanoparticles have potential to be targeted to cancer cells and locally boost radiation effects, with promise to improve the therapeutic ratio. Gadolinium-based nanoparticles (GdBNPs) are promising due to their radiation enhancing properties and ability to enhance tumour imaging via magnetic resonance imaging (MRI). However, the mechanisms behind nanoparticle (NP) microdistribution and their impact on radiation enhancement remain poorly understood. This thesis presents an in vitro spheroid and imaging platform for quantifying GdBNP uptake, mapping GdBNP distribution, with application demonstration in NP-enhanced radiotherapy (NERT). This thesis focuses on the development of the platform, designed to provide a foundation for future therapeutic studies. Optimised histology protocols for both frozen (required to preserve NP fluorescence signal) and formalin-fixed paraffin embedded (FFPE) (conventionally used for immunohistochemistry) sections were developed, enabling high-resolution mapping of NP uptake and cell status (proliferation and hypoxia). By varying seeding number and culture duration, spheroid size, and distribution of HIF1α and Ki67 could be controlled, enabling a platform with controllable distribution of hypoxia and proliferation towards investigating the impact of these distributions on NP uptake. Fluorescence imaging was identified as the most effective technique for mapping NP distribution, and image analysis pipelines that co-localise NP uptake with cell status were developed. The platform was used to study factors impacting NP uptake and distribution, showing that incubation time, rather than concentration, significantly influenced NP penetration depth. Additionally, NP uptake and distribution may depend on the microenvironment cell status in the spheroid model, with hypoxia enhancing NP uptake only within a certain range of hypoxic level. However, further study is required to validate this hypothesis. Bioinformatics pipelines using Gene Set Enrichment Analysis (GSEA) were developed to investigate NERT mechanisms. Preliminary analysis of irradiated U87 cells treated with NPs revealed key pathways related to DNA damage, repair, and immune response. Although integration into radiation studies is ongoing, this platform provides a controllable tool for exploring NP-cell and NP-radiation interactions. These advancements offer critical insights for optimising NERT and improving cancer treatments.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | A nanoparticle uptake platform for characterisation of nanoparticle-enhanced radiotherapy |
| Language: | English |
| Additional information: | Copyright © The Author 2025. 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 > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10203062 |
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