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Biomaterial-based transdermal and implantable vaccine delivery systems for cancer immunotherapy / SAUL MICHUE-SEIJAS

Swansea University Author: SAUL MICHUE-SEIJAS

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DOI (Published version): 10.23889/SUthesis.61815

Abstract

Activating the immune system to target cancer cells is one of the most promising and novel therapeutic approaches for cancer treatment. It offers the potential for long-term protection and limiting off-target cytotoxicity in healthy tissue, which are some of the major drawbacks in chemotherapy. Howe...

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Published: Swansea 2022
Institution: Swansea University
Degree level: Doctoral
Degree name: Ph.D
Supervisor: Mareque-Rivas, Juan
URI: https://cronfa.swan.ac.uk/Record/cronfa61815
first_indexed 2022-11-08T11:49:41Z
last_indexed 2023-01-13T19:22:49Z
id cronfa61815
recordtype RisThesis
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spelling 2022-11-08T12:00:26.2700434 v2 61815 2022-11-08 Biomaterial-based transdermal and implantable vaccine delivery systems for cancer immunotherapy ba6f0e74fc4f3935e732d29910ec1a0f SAUL MICHUE-SEIJAS SAUL MICHUE-SEIJAS true false 2022-11-08 Activating the immune system to target cancer cells is one of the most promising and novel therapeutic approaches for cancer treatment. It offers the potential for long-term protection and limiting off-target cytotoxicity in healthy tissue, which are some of the major drawbacks in chemotherapy. However, limited patient response and autoimmune adverse effects remain current challenges in cancer immunotherapy. The administration of immunotherapies and combination therapies into the immune cell-rich dermal skin region using biodegradable microneedles or into the tumour resection site using implants could overcome these limitations by stimulating a local and controlled therapeutic response. This thesis presents the development and functionalisation of biomaterial-based microneedles and implantable devices to promote the sustained delivery of a variety of immunomodulatory drugs and anticancer agents into the microenvironment of the tumour aiming to locally modulate the immune response. Specifically, the covalent functionalisation of hyaluronic acid to a clinically investigated IDO inhibitor, 1-methyltryptophan, was explored as well as the development of a variety of immunomodulatory nano- and microparticle systems including: (i) self-assembled hyaluronic acid nanoparticles incorporating the clinically used immune checkpoint inhibitor, anti-PD-L1; (ii) immunostimulatory vaccine functionalised iron oxide nanoparticles, (iii) a Pt(IV) prodrug decorated iron oxide nanoparticle system for immunochemotherapy; and (iv) multimodal biosilica-based constructs showing intrinsic peroxidase-like activity and biosensor applications. The incorporation of some of these systems into microneedles and implantable devices demonstrated gradual drug release under physiological conditions and retention of functional activity in vitro using different murine and human cancer cell models. The experimental results highlight the potential of these microneedles and implants as sustained delivery platforms for enhanced cancer immunotherapy and combination therapy. E-Thesis Swansea Cancer immunotherapy, nanomedicine, microneedles and implants 8 11 2022 2022-11-08 10.23889/SUthesis.61815 ORCiD identifier: https://orcid.org/0000-0002-3633-3283 COLLEGE NANME COLLEGE CODE Swansea University Mareque-Rivas, Juan Doctoral Ph.D Swansea University 2022-11-08T12:00:26.2700434 2022-11-08T11:47:10.9881336 Faculty of Science and Engineering School of Engineering and Applied Sciences - Chemistry SAUL MICHUE-SEIJAS 1 61815__25690__0fafd18a9ca445e28e1a7d5531c70438.pdf Michue-Seijas_Saul_Ph_Thesis_Final_Embargoed_Redacted_Signature.pdf 2022-11-08T11:56:02.5193821 Output 12053959 application/pdf E-Thesis – open access true 2024-11-08T00:00:00.0000000 Copyright: The author, Saul Michue Seijas, 2022. true eng
title Biomaterial-based transdermal and implantable vaccine delivery systems for cancer immunotherapy
spellingShingle Biomaterial-based transdermal and implantable vaccine delivery systems for cancer immunotherapy
SAUL MICHUE-SEIJAS
title_short Biomaterial-based transdermal and implantable vaccine delivery systems for cancer immunotherapy
title_full Biomaterial-based transdermal and implantable vaccine delivery systems for cancer immunotherapy
title_fullStr Biomaterial-based transdermal and implantable vaccine delivery systems for cancer immunotherapy
title_full_unstemmed Biomaterial-based transdermal and implantable vaccine delivery systems for cancer immunotherapy
title_sort Biomaterial-based transdermal and implantable vaccine delivery systems for cancer immunotherapy
author_id_str_mv ba6f0e74fc4f3935e732d29910ec1a0f
author_id_fullname_str_mv ba6f0e74fc4f3935e732d29910ec1a0f_***_SAUL MICHUE-SEIJAS
author SAUL MICHUE-SEIJAS
author2 SAUL MICHUE-SEIJAS
format E-Thesis
publishDate 2022
institution Swansea University
doi_str_mv 10.23889/SUthesis.61815
college_str Faculty of Science and Engineering
hierarchytype
hierarchy_top_id facultyofscienceandengineering
hierarchy_top_title Faculty of Science and Engineering
hierarchy_parent_id facultyofscienceandengineering
hierarchy_parent_title Faculty of Science and Engineering
department_str School of Engineering and Applied Sciences - Chemistry{{{_:::_}}}Faculty of Science and Engineering{{{_:::_}}}School of Engineering and Applied Sciences - Chemistry
document_store_str 1
active_str 0
description Activating the immune system to target cancer cells is one of the most promising and novel therapeutic approaches for cancer treatment. It offers the potential for long-term protection and limiting off-target cytotoxicity in healthy tissue, which are some of the major drawbacks in chemotherapy. However, limited patient response and autoimmune adverse effects remain current challenges in cancer immunotherapy. The administration of immunotherapies and combination therapies into the immune cell-rich dermal skin region using biodegradable microneedles or into the tumour resection site using implants could overcome these limitations by stimulating a local and controlled therapeutic response. This thesis presents the development and functionalisation of biomaterial-based microneedles and implantable devices to promote the sustained delivery of a variety of immunomodulatory drugs and anticancer agents into the microenvironment of the tumour aiming to locally modulate the immune response. Specifically, the covalent functionalisation of hyaluronic acid to a clinically investigated IDO inhibitor, 1-methyltryptophan, was explored as well as the development of a variety of immunomodulatory nano- and microparticle systems including: (i) self-assembled hyaluronic acid nanoparticles incorporating the clinically used immune checkpoint inhibitor, anti-PD-L1; (ii) immunostimulatory vaccine functionalised iron oxide nanoparticles, (iii) a Pt(IV) prodrug decorated iron oxide nanoparticle system for immunochemotherapy; and (iv) multimodal biosilica-based constructs showing intrinsic peroxidase-like activity and biosensor applications. The incorporation of some of these systems into microneedles and implantable devices demonstrated gradual drug release under physiological conditions and retention of functional activity in vitro using different murine and human cancer cell models. The experimental results highlight the potential of these microneedles and implants as sustained delivery platforms for enhanced cancer immunotherapy and combination therapy.
published_date 2022-11-08T14:25:28Z
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score 11.048064

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