20.500.12556/RUL-182891 Silica-coated SPIONs induce ferroptosis in endothelial cells while oleic acid mitigates their cytotoxic effects Purpose: Induction of ferroptosis, a form of cell death driven by iron-dependent lipid peroxidation, holds promise as a novel cancer therapy. Superparamagnetic iron oxide nanoparticles (SPIONs) have been proven able to induce ferroptosis in tumour cells, while their effects on non-cancerous cells remain unclear. In this study, we investigated the ability of silica-coated SPIONs to induce ferroptosis in human umbilical vein endothelial cells (HUVEC) and explored the potential protective effects of oleic acid (OA). Additionally, we evaluated the applicability of scanning electron microscopy (SEM) in distinguishing between ferroptotic and apoptotic cell death. Results: We confirmed that silica-coated SPIONs, (used at concentrations of 25 and 50 μg/mL) increased lipid peroxidation and ROS formation in a dose-dependent manner up to 4.9- and 4-fold compared to controls, ultimately promoting ferroptosis without evidence of apoptosis, as indicated by the absence of phosphatidylserine-positive, propidium iodide-negative cells in flow cytometry experiments. Consistent with these results, the ferroptosis inhibitors α-tocopherol and ferrostatin-1 attenuated SPION-induced cytotoxicity, supporting ferroptosis as the primary mechanism of cell death. OA also protected cells from SPION-induced cytotoxicity by reducing lipid peroxidation, ROS formation, and cell death (from 58% to 26%), while increasing glutathione peroxidase expression. Unfortunately, due to the similar surface morphology of ferroptotic and apoptotic cells, SEM is not a reliable method for distinguishing between these two forms of cell death. Conclusion: This study provides important insights into the mechanisms of toxicity of silica-coated SPIONs in endothelial cells and highlights the potential role of OA as a modulator of SPION-induced side effects. SPION oleic acid GPX4 ROS ferroptosis lipid peroxidation superparamagnetni železovi oksidni nanodelci oleinska kislina glutation peroksidaza 4 reaktivne kisikove zvrsti feroptoza peroksidacija lipidov true false true Angleški jezik Slovenski jezik Članek v reviji 2026-05-27 10:45:02 2026-05-27 10:45:04 2026-05-28 04:33:37 0000-00-00 00:00:00 2025 0 0 Str. 15441-15459 Vol. 20 2025 0000-00-00 Zaloznikova Objavljeno apc 0000-00-00 0000-00-00 0000-00-00 577 1178-2013 10.2147/IJN.S548090 264236291 RAZ_Repar_Neza_2025.pdf RAZ_Repar_Neza_2025.pdf 1 D1207266043D823892E7F52D3119D3C3 3a8c4852d7b3e521434c7ea828c4a485021969aa06af7cfa45004023bf1b7ae3 56f43977-59a8-11f1-b0ab-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=234533 https://www.dovepress.com/silica-coated-spions-induce-ferroptosis-in-endothelial-cells-while-ole-peer-reviewed-fulltext-article-IJN 0 502df85a-59a8-11f1-b0ab-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=234532 Biotehniška fakulteta Fakulteta za farmacijo 0 0 0