|
Title
|
|
|
|
Cold plasma-treated hydrogels for multimodal cancer therapy
| |
|
Author
|
|
|
|
| |
|
Abstract
|
|
|
|
| Cold atmospheric plasma (hereon just plasma), the weakly ionized gas and a fourth state of matter, could drive advances in oncology. It generates reactive oxygen and nitrogen species (RONS) and could be used to target the altered redox metabolism in malignant cells. However, the technology faces challenges, particularly in hard-to-reach internal tumors. To help overcome the limitations related to plasma application and accelerate its clinical translation, this Thesis investigates Plasma-Treated Hydrogels (PTHs) as vehicles for the local delivery of plasma-derived RONS to internal targets. Importantly, PTHs could act not only as RONS vehicles but also as a versatile physicochemical platform that incorporates different bioactive polymers or drugs for combinatorial therapeutic approaches, as explored for the first time in this Thesis. This Thesis proposes and follows an iterative workflow cycle for the development and characterization of PTHs. Alginate was chosen as a biopolymer for the preparation of PTHs, due to its favorable properties and mild crosslinking conditions. In the first place, the protocol for the preparation of alginate-based PTHs was optimized, to prevent the loss of therapeutic RONS and obtain an injectable and shear-thinning material capable of adapting to irregular shapes within the body, allowing for both minimally invasive (non-surgical) and post-surgical applications (e.g., to prevent local recurrence). Before this Thesis, biological characterization of PTHs was limited to cancer cytotoxicity reports. Here, the ability of a PTH to also promote antitumor immune responses was investigated, observing enhanced phagocytosis of PTH-treated osteosarcoma cells by monocyte-derived immature dendritic cells. Next, the feasibility and efficacy of incorporating a secondary therapeutic modality to a PTH were investigated. A bioactive polymer or a chemotherapeutic drug was introduced into the alginate PTH, achieving biological effects beyond or in synergy with RONS. Importantly, these effects were studied in ovo (in egg), where three-dimensional and vascularized tumors were grown on the chorioallantoic membrane to observe cancer cells in an environment more similar to a native, clinical one. Unlike mono-therapies with PTH or drug alone, which had no effect in ovo, single administration of PTH-drug co-therapy diminished osteosarcoma tumor weight and significantly reduced the expression of a protein linked to therapy resistance. Altogether, the work presented in this PhD Thesis helped establish PTHs as a novel plasma modality within the community and provided a proof of concept and rationale for their use as versatile dual platforms and in combination with existing therapies for multimodal cancer management. |
| |
|
Language
|
|
|
|
English
| |
|
Publication
|
|
|
|
Barcelona
:
Universitat Politècnica de Catalunya & University of Antwerp
,
2025
| |
|
DOI
|
|
|
|
10.63028/10067/2126460151162165141
| |
|
Volume/pages
|
|
|
|
181 p.
| |
|
Note
|
|
|
|
:
Canal, Cristina [Supervisor]
:
Espona-Noguera, Albert [Supervisor]
:
Bogaerts, Annemie [Supervisor]
:
Lin, Abraham [Supervisor]
| |
|
Full text (open access)
|
|
|
|
|
The publisher created published version Available from 04.04.2026
|
| |
|