E-Thesis 418 views
Biomaterial-based transdermal and implantable vaccine delivery systems for cancer immunotherapy / SAUL MICHUE-SEIJAS
Swansea University Author: SAUL MICHUE-SEIJAS
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...
| Published: |
Swansea
2022
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| Institution: | Swansea University |
| Degree level: | Doctoral |
| Degree name: | Ph.D |
| Supervisor: | Mareque-Rivas, Juan |
| URI: | https://cronfa.swan.ac.uk/Record/cronfa61815 |
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| 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. 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. |
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| Item Description: |
ORCiD identifier: https://orcid.org/0000-0002-3633-3283 |
| Keywords: |
Cancer immunotherapy, nanomedicine, microneedles and implants |
| College: |
Faculty of Science and Engineering |