2026-04-14T03:46:56Zhttps://recercat.cat/oai/request

oai:recercat.cat:2117/4463952026-02-07T05:23:15Zcom_2072_1033col_2072_452950

00925njm 22002777a 4500 dc Živanić, Milica author Espona Noguera, Albert author Privat Maldonado, Angela author Matušu, Patrik author Tampieri, Francesco author Ginebra Molins, Maria Pau author Lin, Abraham author Smits, Evelien author Bogaerts, Annemie author Canal Barnils, Cristina author 2025-08-14 Oxidative stress-based therapies exploit common cancer traits—elevated reactive oxygen species and altered redox metabolism,—making tumors more susceptible to oxidative damage from, e.g., cold atmospheric plasma, an ionized gas containing reactive oxygen and nitrogen species (RONS). Plasma-treated hydrogels (PTH) emerge as vehicles for RONS delivery. Here, PTH are explored as single vehicle for the combined local delivery of RONS and Doxorubicin (Dox). Dox does not impair PTH function, and its IC50 is lowered in vitro; biological characterization and monotherapy comparison are conducted in ovo. Analysis of over 200 tumors, derived from liposarcoma SW872 or osteosarcoma 143B cell lines, reveals effects in the latter after a single PTH-Dox administration: synergistic GPX4 reduction, with the fraction of high cytoplasmic GPX4 cells dropping from 47% to 24%, and diminished average tumor weight, with multiple tumors (of smaller initial size) weighting 70% less than control. In contrast, mono-therapies enhanced the protective GPX4/NRF2 mRNA or protein expression. GPX4 is a ferroptosis inhibitor linked to therapy resistance. Observing effects after a single PTH-Dox hydrogel administration is exceptional, as indirect plasma treatment has until now required frequent dosing in complex tumor models. For clinical use, multimodal approaches are key, and PTHs offer a convenient platform. The authors acknowledge Instituto de Salud Carlos III (ISCIII) and Next Generation EU funds through Project IHRC22/00003 SELLO EXCEL. ISCIII-HEALTH and MINECO though Project PID2022-141120OB-I00 funded by MCIU/AEI/10.13039/501100011033/FEDER, UE. MZ, AEN, and CC belong to the SGR2022-1368. Support for the research of CC was received through the ICREA Academia Award for excellence in research, funded by the Generalitat de Catalunya. The authors thank Generalitat de Catalunya for the Scholarship of MZ (2022 FI_B 00532) and COST Action CA20114 (Therapeutical Applications of Cold Plasmas) for the stimulating environment provided and for funding MZ's short-term scientific mission. This work was also partially funded by the Research Foundation—Flanders (FWO) and supported by the following Grant: G004524N (AB and APM) and by a donation of Dedert Schilde vzw (ES) Peer Reviewed Postprint (published version) Àrees temàtiques de la UPC::Enginyeria biomèdica::Biomaterials::Polímers en medicina Cold plasma Combinatorial treatment Doxorubicin Drug delivery Ferroptosis Sarcoma Plasma-treated hydrogel for combined RONS and chemotherapy delivery: a proof-of-concept in Ovo