{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T16:19:25Z","timestamp":1780935565760,"version":"3.54.1"},"reference-count":54,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T00:00:00Z","timestamp":1663718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["105994"],"award-info":[{"award-number":["105994"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Titanium dioxide nanoparticles (TiO2NPs) are found in a wide range of products such as sunscreen, paints, toothpaste and cosmetics due to their white pigment and high refractive index. These wide-ranging applications could result in direct or indirect exposure of these NPs to humans and the environment. Accordingly, conflicting levels of toxicity has been associated with these NPs. Therefore, the risk associated with these reports and for TiO2NPs produced using varying methodologies should be measured. This study aimed to investigate the effects of various media on TiO2NP properties (hydrodynamic size and zeta potential) and the effects of TiO2NP exposure on human colorectal adenocarcinoma (Caco-2) epithelial cell viability, inflammatory and cell stress biomarkers and angiogenesis proteome profiles. The NPs increased in size over time in the various media, while zeta potentials were stable. TiO2NPs also induced cell stress biomarkers, which could be attributed to the NPs not being cytotoxic. Consequently, TiO2NP exposure had no effects on the level of inflammatory biomarkers produced by Caco-2. TiO2NPs expressed some anti-angiogenic properties when exposed to the no-observed-adverse-effect level and requires further in-depth investigation.<\/jats:p>","DOI":"10.3390\/biom12101334","type":"journal-article","created":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T21:22:23Z","timestamp":1663795343000},"page":"1334","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The Stability and Anti-Angiogenic Properties of Titanium Dioxide Nanoparticles (TiO2NPs) Using Caco-2 Cells"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9190-8978","authenticated-orcid":false,"given":"Oladipupo Moyinoluwa","family":"David","sequence":"first","affiliation":[{"name":"Department of Medical Bioscience, University of the Western Cape, Cape Town 7535, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4772-794X","authenticated-orcid":false,"given":"Kim Leigh","family":"Lategan","sequence":"additional","affiliation":[{"name":"Department of Medical Bioscience, University of the Western Cape, Cape Town 7535, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6627-4504","authenticated-orcid":false,"given":"Maria Fidalgo","family":"de Cortalezzi","sequence":"additional","affiliation":[{"name":"Department of Civil and Environmental Engineering, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edmund John","family":"Pool","sequence":"additional","affiliation":[{"name":"Department of Medical Bioscience, University of the Western Cape, Cape Town 7535, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S0254-0584(02)00343-7","article-title":"Bandgap studies on anatase titanium dioxide nanoparticles","volume":"78","author":"Reddy","year":"2003","journal-title":"Mater. Chem. Phys."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/1743-8977-10-15","article-title":"Titanium dioxide nanoparticles: A review of current toxicological data","volume":"10","author":"Shi","year":"2013","journal-title":"Part. Fibre Toxicol."},{"key":"ref_3","first-page":"481","article-title":"Toxicological effects of titanium dioxide nanoparticles: A review of in vitro mammalian studies","volume":"15","author":"Iavicoli","year":"2011","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1615\/CritRevTherDrugCarrierSyst.2013006955","article-title":"Peptide and protein delivery using new drug delivery systems","volume":"30","author":"Jain","year":"2013","journal-title":"Critical Reviews\u2122 in Therapeutic Drug Carrier Systems"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ziental, D., Czarczynska-Goslinska, B., Mlynarczyk, D.T., Glowacka-Sobotta, A., Stanisz, B., Goslinski, T., and Sobotta, L. (2020). Titanium dioxide nanoparticles: Prospects and applications in medicine. Nanomaterials, 10.","DOI":"10.20944\/preprints202002.0271.v1"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1007\/s12011-019-01706-6","article-title":"Effects of Titanium Dioxide Nanoparticles Exposure on Human Health-a Review","volume":"193","author":"Szwajgier","year":"2020","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1002\/jat.1414","article-title":"In vivo acute toxicity of titanium dioxide nanoparticles to mice after intraperitioneal injection","volume":"29","author":"Chen","year":"2009","journal-title":"J. Appl. Toxicol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"111978","DOI":"10.1016\/j.ecoenv.2021.111978","article-title":"Synthesis, characterization and advanced sustainable applications of titanium dioxide nanoparticles: A review","volume":"212","author":"Irshad","year":"2021","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Musial, J., Krakowiak, R., Mlynarczyk, D.T., Goslinski, T., and Stanisz, B.J. (2020). Titanium dioxide nanoparticles in food and personal care products\u2014What do we know about their safety?. Nanomaterials, 10.","DOI":"10.3390\/nano10061110"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/1743-8977-10-9","article-title":"Comparative absorption, distribution, and excretion of titanium dioxide and zinc oxide nanoparticles after repeated oral administration","volume":"10","author":"Cho","year":"2013","journal-title":"Part. Fibre Toxicol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.toxlet.2014.04.014","article-title":"Cell uptake and oral absorption of titanium dioxide nanoparticles","volume":"228","author":"Janer","year":"2014","journal-title":"Toxicol. Lett."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.toxlet.2011.04.034","article-title":"Tissue distribution and excretion of intravenously administered titanium dioxide nanoparticles","volume":"205","author":"Xie","year":"2011","journal-title":"Toxicol. Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"8784","DOI":"10.1158\/0008-5472.CAN-09-2496","article-title":"Titanium dioxide nanoparticles induce DNA damage and genetic instability in vivo in mice","volume":"69","author":"Trouiller","year":"2009","journal-title":"Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.fct.2013.12.018","article-title":"TiO(2) nanoparticles and bulk material stimulate human peripheral blood mononuclear cells","volume":"65","author":"Becker","year":"2014","journal-title":"Food Chem. Toxicol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Chen, E.Y., Garnica, M., Wang, Y.C., Chen, C.S., and Chin, W.C. (2011). Mucin secretion induced by titanium dioxide nanoparticles. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016198"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.jfda.2014.01.008","article-title":"Genotoxicity of titanium dioxide nanoparticles","volume":"22","author":"Chen","year":"2014","journal-title":"J. Food Drug Anal."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.tiv.2011.12.011","article-title":"Titanium dioxide nanoparticles induced cytotoxicity, oxidative stress and DNA damage in human amnion epithelial (WISH) cells","volume":"26","author":"Saquib","year":"2012","journal-title":"Toxicol. Vitr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.tiv.2014.12.007","article-title":"Oxidative and pro-inflammatory effects of cobalt and titanium oxide nanoparticles on aortic and venous endothelial cells","volume":"29","author":"Alinovi","year":"2015","journal-title":"Toxicol. Vitr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.freeradbiomed.2014.04.026","article-title":"Titanium dioxide nanoparticles induce strong oxidative stress and mitochondrial damage in glial cells","volume":"73","author":"Chirino","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1039\/c2em10746e","article-title":"Impact of agglomeration and different dispersions of titanium dioxide nanoparticles on the human related in vitro cytotoxicity and genotoxicity","volume":"14","author":"Magdolenova","year":"2012","journal-title":"J. Environ. Monit."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"48","DOI":"10.3109\/17435390.2011.629747","article-title":"TiO(2) nanoparticles induce oxidative DNA damage and apoptosis in human liver cells","volume":"7","author":"Shukla","year":"2013","journal-title":"Nanotoxicology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.colsurfb.2011.10.056","article-title":"Physicochemical characterization of engineered nanoparticles under physiological conditions: Effect of culture media components and particle surface coating","volume":"91","author":"Fatisson","year":"2012","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.tiv.2017.06.006","article-title":"Cytotoxicity and immunomodulatory effects of sol-gel combustion based titanium dioxide (TiO2) particles of large surface area on RAW 264.7 macrophages","volume":"43","author":"Dinesh","year":"2017","journal-title":"Toxicol. Vitr."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Aslant\u00fcrk, \u00d6.S. (2018). In Vitro Cytotoxicity and Cell Viability Assays: Principles, Advantages, and Disadvantages, InTech.","DOI":"10.5772\/intechopen.71923"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/S0076-6879(96)68016-1","article-title":"Measurement of Nitrate and Nitrite in Biological Samples Using Nitrate Reductase and Griess Reaction","volume":"Volume 268","author":"Granger","year":"1996","journal-title":"Methods in Enzymology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.toxlet.2014.02.020","article-title":"Genotoxic evaluation of titanium dioxide nanoparticles in vivo and in vitro","volume":"226","author":"Chen","year":"2014","journal-title":"Toxicol. Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.3390\/nano5031163","article-title":"Nanotoxicity: An interplay of oxidative stress, inflammation and cell death","volume":"5","author":"Khanna","year":"2015","journal-title":"Nanomaterials"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3887","DOI":"10.1016\/j.watres.2012.11.061","article-title":"An experimental study on the aggregation of TiO2 nanoparticles under environmentally relevant conditions","volume":"47","author":"Romanello","year":"2013","journal-title":"Water Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7309","DOI":"10.1021\/es100417s","article-title":"Dispersion and stability optimization of TiO2 nanoparticles in cell culture media","volume":"44","author":"Ji","year":"2010","journal-title":"Environ. Sci. Technol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s11051-008-9446-4","article-title":"Characterization of size, surface charge, and agglomeration state of nanoparticle dispersions for toxicological studies","volume":"11","author":"Jiang","year":"2009","journal-title":"J. Nanopart. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"9810","DOI":"10.1016\/j.biomaterials.2011.08.085","article-title":"The effect of particle size on the cytotoxicity, inflammation, developmental toxicity and genotoxicity of silver nanoparticles","volume":"32","author":"Park","year":"2011","journal-title":"Biomaterials"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1038\/s41598-018-19628-z","article-title":"Uptake, distribution, clearance, and toxicity of iron oxide nanoparticles with different sizes and coatings","volume":"8","author":"Feng","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1080\/17435390.2019.1592259","article-title":"Systematic determination of the relationship between nanoparticle core diameter and toxicity for a series of structurally analogous gold nanoparticles in zebrafish","volume":"13","author":"Truong","year":"2019","journal-title":"Nanotoxicology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.tiv.2014.10.023","article-title":"Toxicity, genotoxicity and proinflammatory effects of amorphous nanosilica in the human intestinal Caco-2 cell line","volume":"29","author":"Tarantini","year":"2015","journal-title":"Toxicol. Vitr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s10565-009-9132-z","article-title":"Toxicity and cellular responses of intestinal cells exposed to titanium dioxide","volume":"26","author":"Koeneman","year":"2010","journal-title":"Cell Biol. Toxicol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1023\/B:JMSM.0000021095.36878.1b","article-title":"Effects of nano-scaled particles on endothelial cell function in vitro: Studies on viability, proliferation and inflammation","volume":"15","author":"Peters","year":"2004","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3191","DOI":"10.3748\/wjg.v10.i21.3191","article-title":"Photocatalytic killing effect of TiO2 nanoparticles on Ls-174-t human colon carcinoma cells","volume":"10","author":"Zhang","year":"2004","journal-title":"World J. Gastroenterol. WJG"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Asakura, H., and Kitahora, T. (2018). Antioxidants and Polyphenols in Inflammatory Bowel Disease: Ulcerative Colitis and Crohn Disease. Polyphenols: Prevention and Treatment of Human Disease, Elsevier.","DOI":"10.1016\/B978-0-12-813008-7.00023-0"},{"key":"ref_39","first-page":"88","article-title":"Therapeutic potentials of superoxide dismutase","volume":"12","author":"Younus","year":"2018","journal-title":"Int. J. Health Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"821","DOI":"10.3389\/fnins.2018.00821","article-title":"Heat shock proteins regulatory role in neurodevelopment","volume":"12","author":"Miller","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1146\/annurev.ge.22.120188.003215","article-title":"The heat-shock proteins","volume":"22","author":"Lindquist","year":"1988","journal-title":"Annu. Rev. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5953685","DOI":"10.1155\/2019\/5953685","article-title":"Circulating oxidative stress biomarkers in clinical studies on type 2 diabetes and its complications","volume":"2019","author":"Bigagli","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2402","DOI":"10.1007\/s11051-014-2402-6","article-title":"Titanium dioxide nanoparticles activate IL8-related inflammatory pathways in human colonic epithelial Caco-2 cells","volume":"16","author":"Cossais","year":"2014","journal-title":"J. Nanopart. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.3109\/17435390.2012.741724","article-title":"Comparative study of ZnO and TiO2 nanoparticles: Physicochemical characterisation and toxicological effects on human colon carcinoma cells","volume":"7","author":"Barone","year":"2013","journal-title":"Nanotoxicology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1080\/10934520903263231","article-title":"Aggregation and toxicity of titanium dioxide nanoparticles in aquatic environment\u2014A review","volume":"44","author":"Sharma","year":"2009","journal-title":"J. Environ. Sci. Health Part A"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4729","DOI":"10.3748\/wjg.v18.i34.4729","article-title":"Titanium dioxide induced inflammation in the small intestine","volume":"18","author":"Nogueira","year":"2012","journal-title":"World J. Gastroenterol. WJG"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6341","DOI":"10.1016\/j.biomaterials.2009.08.008","article-title":"Antiangiogenic properties of silver nanoparticles","volume":"30","author":"Gurunathan","year":"2009","journal-title":"Biomaterials"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.crohns.2013.06.013","article-title":"Angiopoietins in inflammation and their implication in the development of inflammatory bowel disease. A review","volume":"8","author":"Linares","year":"2014","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"261","DOI":"10.3109\/08977199209046408","article-title":"Platelet-derived growth factor is angiogenic in vivo","volume":"7","author":"Risau","year":"1992","journal-title":"Growth Factors"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e1109","DOI":"10.1016\/j.nano.2014.02.007","article-title":"Anti-angiogenic effect of bare titanium dioxide nanoparticles on pathologic neovascularization without unbearable toxicity","volume":"10","author":"Jo","year":"2014","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2422","DOI":"10.1016\/j.bbagen.2015.09.007","article-title":"Endostatin\u2019s emerging roles in angiogenesis, lymphangiogenesis, disease, and clinical applications","volume":"1850","author":"Walia","year":"2015","journal-title":"Biochim. Et Biophys. Acta (BBA)-Gen. Subj."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1038\/bjc.2011.348","article-title":"Activin A inhibits vascular endothelial cell growth and suppresses tumour angiogenesis in gastric cancer","volume":"105","author":"Kaneda","year":"2011","journal-title":"Br. J. Cancer"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Kitlinska, J., Lee, E.W., Li, L., Pons, J., Estes, L., and Zukowska, Z. (2004). Dual role of dipeptidyl peptidase IV (DPP IV) in angiogenesis and vascular remodeling. Dipeptidyl Aminopeptidases in Health and Disease, Springer.","DOI":"10.1007\/0-306-47920-6_26"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"213","DOI":"10.2147\/vhrm.2006.2.3.213","article-title":"Angiogenesis in cancer","volume":"2","author":"Nishida","year":"2006","journal-title":"Vasc. Health Risk Manag."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/10\/1334\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:36:26Z","timestamp":1760142986000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/10\/1334"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,21]]},"references-count":54,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["biom12101334"],"URL":"https:\/\/doi.org\/10.3390\/biom12101334","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,21]]}}}