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Chemically programming redox-active nanovaccines and theranostic nanoparticles for combination cancer immunotherapy / Marc Bilbao-Asensio

Swansea University Author: Marc Bilbao-Asensio

  • E-Thesis – open access under embargo until: 17th June 2025

DOI (Published version): 10.23889/SUthesis.60304

Abstract

Cancer immunotherapies have established their relevance in the clinic in recent years. These therapies have increased patient survival rates with few toxic side-effects. However, they still suffer from low patient response rates. With the progression of the disease, tumors become increasingly hetero...

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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/cronfa60304
first_indexed 2022-06-22T16:11:25Z
last_indexed 2022-06-29T03:20:24Z
id cronfa60304
recordtype RisThesis
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spelling 2022-06-28T12:43:47.5454496 v2 60304 2022-06-22 Chemically programming redox-active nanovaccines and theranostic nanoparticles for combination cancer immunotherapy 4ae8c2bb4cded4b2f32a3946790b9e46 Marc Bilbao-Asensio Marc Bilbao-Asensio true false 2022-06-22 Cancer immunotherapies have established their relevance in the clinic in recent years. These therapies have increased patient survival rates with few toxic side-effects. However, they still suffer from low patient response rates. With the progression of the disease, tumors become increasingly heterogeneous, which poses limits to the development of universal, “off the shelf” cures. Nanotechnology allows insight over novel therapy strategies to better suit the specificities and uniqueness of each patient’s cancer. In this work, a chemistry and material science approach enabled the development of iron oxide nanoparticle-filled nanovaccines (IONVs) to exploit the biochemical features of the tumor microenvironment for cancer immunotherapy and combination therapy. A systematic nanoparticle engineering rationale is stablished to “programme” IONVs for: (i) cancer cell sensitization to oxidative damage and ferroptosis; (ii) pH-catalysed disassembly and drug release; (iii) macrophage repolarization towards tumor-suppressing phenotypes; (iv) optimization of tumor-antigen processing and cross-presentation; (v) optimization of platinum-based prodrug delivery for chemotherapy and chemoimmunotherapy; (vi) integration of directing ligands for active targeted drug delivery; (vii) monitorable therapy biodistribution; and (viii) synergy with state-of-the-art antibody-based immunotherapies.Systematic IONV engineering provided control over distinguishable device properties such as size, charge, stability, chemical reactivity, bioactive molecule loading and particle surface functionalization. The device integrated iron catalysis for cancer-cell specific activation of ferroptosis, immunostimulatory redox stress and site-specific disassembly for targeted drug release. IONVs were visualized to accumulate into the tumor tissue as well as immune cell-rich tissues such as spleen and lymph nodes. Their high biocompatibility enabled immune cell activation for multipronged antitumor action. The results show how IONVs can unite and improve concurrently effective anticancer strategies, resulting in complete elimination of established aggressive tumors and acquisition of protective long-term immunity. Overall, this work demonstrates the suitability of programmable IONVs to act as generalizable platforms for cancer immunotherapy enhancement. E-Thesis Swansea Chemistry, Immunotherapy, Oncology, Nanomedicine 17 6 2022 2022-06-17 10.23889/SUthesis.60304 ORCiD identifier: https://orcid.org/0000-0002-2862-403X COLLEGE NANME COLLEGE CODE Swansea University Mareque-Rivas, Juan Doctoral Ph.D EPSRC doctoral training grant; Grant No: 2105067 (related to EP/N509553/1) 2022-06-28T12:43:47.5454496 2022-06-22T17:02:04.8162076 Faculty of Science and Engineering School of Engineering and Applied Sciences - Chemistry Marc Bilbao-Asensio 1 Under embargo Under embargo 2022-06-22T17:18:25.6893786 Output 12095706 application/pdf E-Thesis – open access true 2025-06-17T00:00:00.0000000 Copyright: The author, Marc Bilbao Asensio, 2022. true eng
title Chemically programming redox-active nanovaccines and theranostic nanoparticles for combination cancer immunotherapy
spellingShingle Chemically programming redox-active nanovaccines and theranostic nanoparticles for combination cancer immunotherapy
Marc Bilbao-Asensio
title_short Chemically programming redox-active nanovaccines and theranostic nanoparticles for combination cancer immunotherapy
title_full Chemically programming redox-active nanovaccines and theranostic nanoparticles for combination cancer immunotherapy
title_fullStr Chemically programming redox-active nanovaccines and theranostic nanoparticles for combination cancer immunotherapy
title_full_unstemmed Chemically programming redox-active nanovaccines and theranostic nanoparticles for combination cancer immunotherapy
title_sort Chemically programming redox-active nanovaccines and theranostic nanoparticles for combination cancer immunotherapy
author_id_str_mv 4ae8c2bb4cded4b2f32a3946790b9e46
author_id_fullname_str_mv 4ae8c2bb4cded4b2f32a3946790b9e46_***_Marc Bilbao-Asensio
author Marc Bilbao-Asensio
author2 Marc Bilbao-Asensio
format E-Thesis
publishDate 2022
institution Swansea University
doi_str_mv 10.23889/SUthesis.60304
college_str Faculty of Science and Engineering
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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
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description Cancer immunotherapies have established their relevance in the clinic in recent years. These therapies have increased patient survival rates with few toxic side-effects. However, they still suffer from low patient response rates. With the progression of the disease, tumors become increasingly heterogeneous, which poses limits to the development of universal, “off the shelf” cures. Nanotechnology allows insight over novel therapy strategies to better suit the specificities and uniqueness of each patient’s cancer. In this work, a chemistry and material science approach enabled the development of iron oxide nanoparticle-filled nanovaccines (IONVs) to exploit the biochemical features of the tumor microenvironment for cancer immunotherapy and combination therapy. A systematic nanoparticle engineering rationale is stablished to “programme” IONVs for: (i) cancer cell sensitization to oxidative damage and ferroptosis; (ii) pH-catalysed disassembly and drug release; (iii) macrophage repolarization towards tumor-suppressing phenotypes; (iv) optimization of tumor-antigen processing and cross-presentation; (v) optimization of platinum-based prodrug delivery for chemotherapy and chemoimmunotherapy; (vi) integration of directing ligands for active targeted drug delivery; (vii) monitorable therapy biodistribution; and (viii) synergy with state-of-the-art antibody-based immunotherapies.Systematic IONV engineering provided control over distinguishable device properties such as size, charge, stability, chemical reactivity, bioactive molecule loading and particle surface functionalization. The device integrated iron catalysis for cancer-cell specific activation of ferroptosis, immunostimulatory redox stress and site-specific disassembly for targeted drug release. IONVs were visualized to accumulate into the tumor tissue as well as immune cell-rich tissues such as spleen and lymph nodes. Their high biocompatibility enabled immune cell activation for multipronged antitumor action. The results show how IONVs can unite and improve concurrently effective anticancer strategies, resulting in complete elimination of established aggressive tumors and acquisition of protective long-term immunity. Overall, this work demonstrates the suitability of programmable IONVs to act as generalizable platforms for cancer immunotherapy enhancement.
published_date 2022-06-17T14:20:41Z
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score 11.247077

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