Injectable Plasma-Treated Alginate Hydrogel for Oxidative Stress Delivery to Induce Immunogenic Cell Death in Osteosarcoma

Research Article: Injectable Plasma-Treated Alginate Hydrogel for OxidativeStress Delivery to Induce Immunogenic Cell Death in Osteosarcoma

Authors: Milica Živanic, Albert Espona-Noguera, Hanne Verswyvel, Evelien Smits,Annemie Bogaerts, Abraham Lin, and Cristina Canal*

ABSTRACT

Cold atmospheric plasma (CAP) is a source of cell-damaging oxidant moleculesthat may be used as low-cost cancer treatment with minimal side eﬀects.Liquids treated with cold plasma and enriched with oxidants are a modalityfor non-invasive treatment of internal tumors with cold plasma via injection.However, liquids are easily diluted with body ﬂuids which impedes high andlocalized delivery of oxidants to the target. As an alternative, plasma-treatedhydrogels (PTH) emerge as vehicles for the precise delivery of oxidants. Thisstudy reports an optimal protocol for the preparation of injectable alginate PTHthat ensures the preservation of plasma-generated oxidants. The generation,storage, and release of oxidants from the PTH are assessed. The eﬃcacy of thealginate PTH in cancer treatment is demonstrated in the context of cancer cellcytotoxicity and immunogenicity–release of danger signals and phagocytosisby immature dendritic cells, up to now unexplored for PTH. These are shownin osteosarcoma, a hard-to-treat cancer. The study aims to consolidate PTHas a novel cold plasma treatment modality for non-invasive or postoperativetumor treatment. The results oﬀer a rationale for further explorationof alginate-based PTHs as a versatile platform in biomedical engineering.