Plasma-Activated Hydrogels (PAH) as Carriers of Bioactive Plasma Species reveal cancer-specific Efficacy in Endometrial Cancer Patient-Derived Organoids (PDOs)

Fertility preserving therapy options for Endometrial cancer (EC) gain more and more relevance. EC is increasingly affecting premenopausal patients and its treatment involves in general a total hysterectomy and adjunctive therapies. Reducing treatment invasiveness for premenopausal patients could significantly improve their quality of life (QOL). RONS generated by non-invasive physical plasma (NIPP) are known for their biological effects. This study aimed to investigate the anti-tumor effects of plasma-activated hydrogels (PAH) on patient-derived endometrial cancer organoids (PDO). Cell culture medium was treated with NIPP and then polymerized into a hydrogel, which effectively carried high concentrations of reactive plasma species. EC cell lines and PDOs were treated with varying doses of PAH. The effects on cell proliferation, cytotoxicity, and apoptosis were assessed and compared to those on benign endometrial cells. PAH exhibited cancer-specific anti-proliferative effects on EC cells, which were also confirmed in PDO cultures. Higher tumor grades correlated with increased cytotoxicity upon PAH application. Additionally, PAH treatment induced a cancer-specific rise in early and late apoptosis, as evidenced by Annexin V and Caspase 3/7 assays.

These results indicate that PAH shows promise in mediating cancer-specific anti-proliferative effects on EC, potentially enhancing disease control and improving QOL for patients.