{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:01:34Z","timestamp":1790614894349,"version":"4.1.0"},"reference-count":32,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,9]],"date-time":"2023-04-09T00:00:00Z","timestamp":1680998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004271","name":"Sapienza University","doi-asserted-by":"publisher","award":["Ateneo 2019"],"award-info":[{"award-number":["Ateneo 2019"]}],"id":[{"id":"10.13039\/501100004271","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Nanomaterials are gaining increasing attention as innovative materials in medicine. Among nanomaterials, zinc oxide (ZnO) nanostructures are particularly appealing because of their opto-electrical, antimicrobial, and photochemical properties. Although ZnO is recognized as a safe material and the Zn ion (Zn2+) concentration is strictly regulated at a cellular and systemic level, different studies have demonstrated cellular toxicity of ZnO nanoparticles (ZnO-NPs) and ZnO nanorods (ZnO-NRs). Recently, ZnO-NP toxicity has been shown to depend on the intracellular accumulation of ROS, activation of autophagy and mitophagy, as well as stabilization and accumulation of hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) protein. However, if the same pathway is also activated by ZnO-NRs and how non-cancer cells respond to ZnO-NR treatment, are still unknown. To answer to these questions, we treated epithelial HaCaT and breast cancer MCF-7 cells with different ZnO-NR concentrations. Our results showed that ZnO-NR treatments increased cell death through ROS accumulation, HIF-1\u03b1 and endothelial PAS domain protein 1 (EPAS1) activation, and induction of autophagy and mitophagy in both cell lines. These results, while on one side, confirmed that ZnO-NRs can be used to reduce cancer growth, on the other side, raised some concerns on the activation of a hypoxic response in normal cells that, in the long run, could induce cellular transformation.<\/jats:p>","DOI":"10.3390\/ijms24086971","type":"journal-article","created":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T03:49:29Z","timestamp":1681098569000},"page":"6971","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["ZnO Nanorods Create a Hypoxic State with Induction of HIF-1 and EPAS1, Autophagy, and Mitophagy in Cancer and Non-Cancer Cells"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9466-0047","authenticated-orcid":false,"given":"Michele","family":"Aventaggiato","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University, Viale Regina Elena 324, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adele","family":"Preziosi","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u201cCharles Darwin\u201d, Sapienza University, P.le A. Moro,5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7998-2999","authenticated-orcid":false,"given":"Hossein","family":"Cheraghi Bidsorkhi","sequence":"additional","affiliation":[{"name":"Department of Aerospace, Electrical and Energy Engineering, Sapienza University, Via Eudossiana 18, 00184 Rome, Italy"},{"name":"Research Center for Nanotechnology Applied to Engineering, Sapienza University, Via Eudossiana 18, 00184 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Schifano","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u201cCharles Darwin\u201d, Sapienza University, P.le A. Moro,5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6146-9302","authenticated-orcid":false,"given":"Simone","family":"Vespa","sequence":"additional","affiliation":[{"name":"Center for Advanced Studies and Technology, University \u201cG. D\u2019Annunzio\u201d of Chieti-Pescara, Via Luigi Polacchi 11, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9032-9667","authenticated-orcid":false,"given":"Stefania","family":"Mardente","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University, Viale Regina Elena 324, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Zicari","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University, Viale Regina Elena 324, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6841-8129","authenticated-orcid":false,"given":"Daniela","family":"Uccelletti","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u201cCharles Darwin\u201d, Sapienza University, P.le A. Moro,5, 00185 Rome, Italy"},{"name":"Research Center for Nanotechnology Applied to Engineering, Sapienza University, Via Eudossiana 18, 00184 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0556-2056","authenticated-orcid":false,"given":"Patrizia","family":"Mancini","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University, Viale Regina Elena 324, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5114-6953","authenticated-orcid":false,"given":"Lavinia Vittoria","family":"Lotti","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University, Viale Regina Elena 324, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8160-0803","authenticated-orcid":false,"given":"Maria Sabrina","family":"Sarto","sequence":"additional","affiliation":[{"name":"Department of Aerospace, Electrical and Energy Engineering, Sapienza University, Via Eudossiana 18, 00184 Rome, Italy"},{"name":"Research Center for Nanotechnology Applied to Engineering, Sapienza University, Via Eudossiana 18, 00184 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7128-810X","authenticated-orcid":false,"given":"Marco","family":"Tafani","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University, Viale Regina Elena 324, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.2217\/nnm.14.62","article-title":"Recent progress in multidrug delivery to cancer cells by liposomes","volume":"9","author":"Mo","year":"2014","journal-title":"Nanomedicine"},{"key":"ref_2","first-page":"37","article-title":"Recent advances in ZnO nanostructures and their future perspective","volume":"11","author":"Ravi","year":"2021","journal-title":"Adv. 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