{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T19:41:33Z","timestamp":1771530093885,"version":"3.50.1"},"reference-count":34,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T00:00:00Z","timestamp":1710720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS","award":["20H03476"],"award-info":[{"award-number":["20H03476"]}]},{"DOI":"10.13039\/501100001700","name":"MEXT of Japan","doi-asserted-by":"publisher","award":["20H03476"],"award-info":[{"award-number":["20H03476"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Japan Racing Association","award":["20H03476"],"award-info":[{"award-number":["20H03476"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Toxoplasma gondii is an intracellular parasitic protozoan with a high infection rate in mammals, including humans, and birds. There is no effective vaccine, and treatment relies on antiparasitic drugs. However, existing antiprotozoal drugs have strong side effects and other problems; therefore, new treatment approaches are needed. Metal nanoparticles have attracted increased interest in the biomedical community in recent years because of their extremely high surface area to volume ratio and their unique reactivity that could be exploited for medicinal purposes. Previously, we confirmed the anti-Toxoplasma effects of gold, silver, and platinum nanoparticles, in a growth inhibition test. Here, we asked whether the anti-Toxoplasma effect could be confirmed with less expensive metal nanoparticles, specifically iron oxide nanoparticles (goethite and hematite). To improve the selective action of the nanoparticles, we modified the surface with l-tryptophan as our previous findings showed that the bio-modification of nanoparticles enhances their selectivity against T. gondii. Fourier-Transform Infrared Spectroscopy (FTIR) analysis confirmed the successful coating of the iron oxide nanoparticles with l-tryptophan. Subsequently, cytotoxicity and growth inhibition assays were performed. L-tryptophan-modified nanoparticles showed superior anti-Toxoplasma action compared to their naked nanoparticle counterparts. L-tryptophan enhanced the selective toxicity of the iron oxide nanoparticles toward T. gondii. The bio-modified nanoparticles did not exhibit detectable host cell toxicity in the effective anti-Toxoplasma doses. To elucidate whether reactive oxygen species contribute to the anti-Toxoplasma action of the bio-modified nanoparticles, we added Trolox antioxidant to the assay medium and found that Trolox appreciably reduced the nanoparticle-induced growth inhibition.<\/jats:p>","DOI":"10.3390\/pharmaceutics16030413","type":"journal-article","created":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T06:58:39Z","timestamp":1710745119000},"page":"413","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Goethite and Hematite Nanoparticles Show Promising Anti-Toxoplasma Properties"],"prefix":"10.3390","volume":"16","author":[{"given":"Kosei","family":"Ishii","sequence":"first","affiliation":[{"name":"Laboratory of Sustainable Animal Environment, Graduate School of Agricultural Science, Tohoku University, 232-3 Yomogida, Naruko-onsen, Osaki 989-6711, Miyagi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eiji","family":"Akahoshi","sequence":"additional","affiliation":[{"name":"Department of Electronic Engineering, Graduate School of Engineering, Tohoku University, 6-6-05 Aza-Aoba, Aramaki, Aoba-ku, Sendai 980-8579, Miyagi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9342-8505","authenticated-orcid":false,"given":"Oluyomi Stephen","family":"Adeyemi","sequence":"additional","affiliation":[{"name":"Laboratory of Sustainable Animal Environment, Graduate School of Agricultural Science, Tohoku University, 232-3 Yomogida, Naruko-onsen, Osaki 989-6711, Miyagi, Japan"},{"name":"Department of Biochemistry, Medicinal Biochemistry, Nanomedicine & Toxicology Laboratory, Bowen University, Iwo 232101, Osun State, Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hironori","family":"Bando","sequence":"additional","affiliation":[{"name":"Laboratory of Sustainable Animal Environment, Graduate School of Agricultural Science, Tohoku University, 232-3 Yomogida, Naruko-onsen, Osaki 989-6711, Miyagi, Japan"},{"name":"Department of Parasitology, Asahikawa Medical University, 2-1-1-1 Midorigaoka-Higashi, Asahikawa 078-8510, Hokkaido, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhiro","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Laboratory of Sustainable Animal Environment, Graduate School of Agricultural Science, Tohoku University, 232-3 Yomogida, Naruko-onsen, Osaki 989-6711, Miyagi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6058-4859","authenticated-orcid":false,"given":"Tomoyuki","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Electronic Engineering, Graduate School of Engineering, Tohoku University, 6-6-05 Aza-Aoba, Aramaki, Aoba-ku, Sendai 980-8579, Miyagi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kentaro","family":"Kato","sequence":"additional","affiliation":[{"name":"Laboratory of Sustainable Animal Environment, Graduate School of Agricultural Science, Tohoku University, 232-3 Yomogida, Naruko-onsen, Osaki 989-6711, Miyagi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Torgerson, P.R., Devleesschauwer, B., Praet, N., Speybroeck, N., Willingham, A.L., Kasuga, F., Rokni, M.B., Zhou, X.-N., F\u00e8vre, E.M., and Sripa, B. (2015). World Health Organization Estimates of the Global and Regional Disease Burden of 11 Foodborne Parasitic Diseases, 2010: A Data Synthesis. PLoS Med., 12.","DOI":"10.1371\/journal.pmed.1001920"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1128\/MMBR.64.3.607-623.2000","article-title":"Lytic cycle of Toxoplasma gondii","volume":"64","author":"Black","year":"2000","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.ijpara.2008.10.001","article-title":"Molecular approaches to diversity of populations of apicomplexan parasites","volume":"39","author":"Beck","year":"2009","journal-title":"Int. J. Parasitol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Lai, B.S., and Juhas, M. (2019). Toxoplasma gondii secretory proteins and their role in invasion and pathogenesis. Microbiol. Res., 227.","DOI":"10.1016\/j.micres.2019.06.003"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"65","DOI":"10.3109\/14992020903214053","article-title":"Maternal infection with Toxoplasma gondii in pregnancy and the risk of hearing loss in the offspring","volume":"49","author":"Austeng","year":"2010","journal-title":"Int. J. Audiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1016\/j.cmi.2020.04.014","article-title":"Toxoplasma gondii-specific IgG avidity testing in pregnant women","volume":"26","author":"Garnaud","year":"2020","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1016\/S0140-6736(98)08220-8","article-title":"Mother-to-child transmission of toxoplasmosis: Risk estimates for clinical counselling","volume":"353","author":"Dunn","year":"1999","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1096\/fj.00-0267com","article-title":"Reactive oxygen species (ROS) mediates the mitochondrial-dependent apoptosis induced by transforming growth factor \u00df in fetal hepatocytes","volume":"15","author":"Herrera","year":"2001","journal-title":"FASEB J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1186\/s13071-020-04445-z","article-title":"The life-cycle of Toxoplasma gondii reviewed using animations","volume":"13","author":"Attias","year":"2020","journal-title":"Parasites Vectors"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S0167-7799(00)01536-5","article-title":"Nantotechniques and approaches in biotechnology","volume":"19","author":"Curtis","year":"2001","journal-title":"Trends Biotechnol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1016\/j.tibtech.2023.06.001","article-title":"Iron oxide nanoparticle-based nanocomposites in biomedical application","volume":"41","author":"Yang","year":"2023","journal-title":"Trends Biotechnol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5581","DOI":"10.1128\/AAC.00868-12","article-title":"A focused small-molecule screen identifies 14 compounds with distinct effects on Toxoplasma gondii","volume":"56","author":"Kamau","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"145","DOI":"10.7555\/JBR.28.20130096","article-title":"Evaluation of metal nanoparticles for drug delivery systems","volume":"29","author":"Adeyemi","year":"2015","journal-title":"J. Biomed. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.colsurfb.2011.03.009","article-title":"Plant extract mediated synthesis of silver and gold nanoparticles and its antibacterial activity against clinically isolated pathogens","volume":"85","author":"MubarakAli","year":"2011","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e1701494","DOI":"10.1002\/adhm.201701494","article-title":"Nanomedicine Approaches Against Parasitic Worm Infections","volume":"7","author":"Li","year":"2018","journal-title":"Adv. Healthc. Mater."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S86","DOI":"10.1080\/21691401.2018.1489267","article-title":"Metal nanoparticles restrict the growth of protozoan parasites","volume":"46","author":"Adeyemi","year":"2018","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1248\/cpb.c19-00157","article-title":"Development of Metal Nanoparticle Catalysis toward Drug Discovery","volume":"67","author":"Arisawa","year":"2019","journal-title":"Chem. Pharm. Bull."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"574","DOI":"10.7150\/thno.67184","article-title":"Tailoring noble metal nanoparticle designs to enable sensitive lateral flow immunoassay","volume":"12","author":"Chen","year":"2022","journal-title":"Theranostics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2848","DOI":"10.1128\/AEM.70.5.2848-2853.2004","article-title":"Use of aqueous silver to enhance inactivation of coliphage MS-2 by UV disinfection","volume":"70","author":"Butkus","year":"2004","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"153","DOI":"10.2174\/138161209787002870","article-title":"Targeted drugs and nanomedicine: Present and future","volume":"15","author":"Debbage","year":"2009","journal-title":"Curr. Pharm. Des."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2705","DOI":"10.2147\/IJN.S23883","article-title":"Antileishmanial effect of silver nanoparticles and their enhanced antiparasitic activity under ultraviolet light","volume":"6","author":"Allahverdiyev","year":"2011","journal-title":"Int. J. Nanomed."},{"key":"ref_22","first-page":"593","article-title":"Antiparasitic activity of silver and copper oxide nanoparticles against Entamoeba histolytica and Cryptosporidium parvum cysts","volume":"45","author":"Saad","year":"2015","journal-title":"J. Egypt. Soc. Parasitol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1080\/17435390.2019.1572809","article-title":"Biodistribution and targeting properties of iron oxide nanoparticles for treatments of cancer and iron anemia disease","volume":"13","author":"Alphandery","year":"2019","journal-title":"Nanotoxicology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1177\/014107689008300208","article-title":"Serious adverse drug reactions to pyrimethamine-sulphadoxine, pyrimethamine-dapsone and to amodiaquine in Britain","volume":"83","author":"West","year":"1990","journal-title":"J. R. Soc. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.ijbiomac.2013.09.008","article-title":"Interaction of nanoparticles with arginine kinase from Trypanosoma brucei: Kinetic and mechanistic evaluation","volume":"62","author":"Adeyemi","year":"2013","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Adeyemi, O.S., Ishii, K., and Kato, K. (2023). L-tryptophan-titanium oxide nanoparticles showed selective anti-Toxoplasma gondii activity and improved host biocompatibility. Biomed. Pharmacother., 162.","DOI":"10.1016\/j.biopha.2023.114597"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1128\/EC.00081-14","article-title":"Toxoplasma gondii development of its replicative niche: In its host cell and beyond","volume":"13","author":"Blader","year":"2014","journal-title":"Eukaryot. Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e13768","DOI":"10.1111\/aji.13768","article-title":"Tryptophan metabolism and immune alterations in pregnant Hispanic women with chronic Toxoplasma gondii infection","volume":"90","author":"Prescott","year":"2023","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1038\/s41419-019-1420-9","article-title":"Tryptophan-Kynurenine Pathway Attenuates \u03b2-Catenin-Dependent pro-Parasitic Role of STING-TICAM2-IRF3-IDO1 Signalosome in Toxoplasma gondii Infection","volume":"10","author":"Majumdar","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.parint.2015.05.004","article-title":"In vitro antiparasitic activity of microbial pigments and their combination with phytosynthesized metal nanoparticles","volume":"64","author":"Suryawanshi","year":"2015","journal-title":"Parasitol. Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1166\/jbn.2018.2544","article-title":"Exploring Amino Acid-Capped Nanoparticles for Selective Anti-Parasitic Action and Improved Host Biocompatibility","volume":"14","author":"Adeyemi","year":"2018","journal-title":"J. Biomed. Nanotechnol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.ymeth.2022.08.005","article-title":"Detection and quantification of nanoparticle-induced intracellular ROS in live cells by laser scanning confocal microscopy","volume":"207","author":"Amaldoss","year":"2022","journal-title":"Methods"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.ejphar.2012.06.031","article-title":"An antioxidant Trolox restores decreased oral absorption of cyclosporine A after liver ischemia-reperfusion through distinct mechanisms between CYP3A and P-glycoprotein in the small intestine","volume":"690","author":"Ikemura","year":"2012","journal-title":"Eur. J. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/nature08268","article-title":"Antioxidant and oncogene rescue of metabolic defects caused by loss of matrix attachment","volume":"461","author":"Schafer","year":"2009","journal-title":"Nature"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/16\/3\/413\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:15:07Z","timestamp":1760105707000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/16\/3\/413"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,18]]},"references-count":34,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["pharmaceutics16030413"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics16030413","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,18]]}}}