{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T20:49:43Z","timestamp":1788209383031,"version":"build-2803163510"},"reference-count":55,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,2,2]],"date-time":"2020-02-02T00:00:00Z","timestamp":1580601600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002383","name":"King Saud University","doi-asserted-by":"publisher","award":["RSP-2019\/129"],"award-info":[{"award-number":["RSP-2019\/129"]}],"id":[{"id":"10.13039\/501100002383","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Materials"],"abstract":"<jats:p>Iron oxide\u2013reduced graphene oxide (Fe3O4-RGO) nanocomposites have attracted enormous interest in the biomedical field. However, studies on biological response of Fe3O4-RGO nanocomposites at the cellular and molecular level are scarce. This study was designed to synthesize, characterize, and explore the cytotoxicity of Fe3O4-RGO nanocomposites in human liver (HepG2) cells. Potential mechanisms of cytotoxicity of Fe3O4-RGO nanocomposites were further explored through oxidative stress. Prepared samples were characterized by UV-visible spectrophotometer, X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and energy dispersive spectroscopy. The results demonstrated that RGO induce dose-dependent cytotoxicity in HepG2 cells. However, Fe3O4-RGO nanocomposites were not toxic. We further noted that RGO induce apoptosis in HepG2 cells, as evidenced by mitochondrial membrane potential loss, higher caspase-3 enzyme activity, and cell cycle arrest. On the other hand, Fe3O4-RGO nanocomposites did not alter these apoptotic parameters. Moreover, we observed that RGO increases intracellular reactive oxygen species and hydrogen peroxide while decrease antioxidant glutathione. Again, Fe3O4-RGO nanocomposites did not exert oxidative stress. Altogether, we found that RGO significantly induced cytotoxicity, apoptosis and oxidative stress. However, Fe3O4-RGO nanocomposites showed good biocompatibility to HepG2 cells. This study warrants further research to investigate the biological response of Fe3O4-RGO nanocomposites at the gene and molecular level.<\/jats:p>","DOI":"10.3390\/ma13030660","type":"journal-article","created":{"date-parts":[[2020,2,3]],"date-time":"2020-02-03T11:28:31Z","timestamp":1580729311000},"page":"660","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Investigation of Cytotoxicity, Apoptosis, and Oxidative Stress Response of Fe3O4-RGO Nanocomposites in Human Liver HepG2 cells"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6025-1950","authenticated-orcid":false,"given":"Maqusood","family":"Ahamed","sequence":"first","affiliation":[{"name":"King Abdullah Institute for Nanotechnology, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9596-7745","authenticated-orcid":false,"given":"Mohd Javed","family":"Akhtar","sequence":"additional","affiliation":[{"name":"King Abdullah Institute for Nanotechnology, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. A. Majeed","family":"Khan","sequence":"additional","affiliation":[{"name":"King Abdullah Institute for Nanotechnology, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1126\/science.1158877","article-title":"Graphene: Status and prospects","volume":"324","author":"Geim","year":"2009","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1126\/science.1150878","article-title":"Chemically derived, ultrasmooth graphene nanoribbon semiconductors","volume":"319","author":"Li","year":"2008","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2930","DOI":"10.1016\/j.biomaterials.2011.01.002","article-title":"A graphene functionalized electrochemical aptasensor for selective label-free detection of cancer cells","volume":"32","author":"Feng","year":"2011","journal-title":"Biomaterials"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"7214","DOI":"10.1039\/C3TA15426B","article-title":"Fe3O4\/reduced graphene oxide with enhanced electrochemical performance towards lithium storage","volume":"2","author":"Liang","year":"2014","journal-title":"J. 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