{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T23:59:35Z","timestamp":1792627175239,"version":"4.5.0"},"reference-count":59,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T00:00:00Z","timestamp":1704931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T00:00:00Z","timestamp":1704931200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2024,1,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            This study aimed to prepare and assess atovaquone (ATQ)-loaded exosomes (EXO-ATQ) against\n            <jats:italic>Toxoplasma gondii<\/jats:italic>\n            to improve their therapeutic activities on acute and chronic phases of murine toxoplasmosis. Exosomes were isolated from a mouse macrophage cell line (J774A.1). The isolated exosomes were loaded with ATQ (EXO-ATQ), applying the co-incubation method.\n            <jats:italic>In vitro<\/jats:italic>\n            efficacy of EXO-ATQ against\n            <jats:italic>T. gondii<\/jats:italic>\n            infection was assessed in Vero cell culture. An\n            <jats:italic>in vivo<\/jats:italic>\n            experiment was carried out in BALB\/c mice infected with RH (acute strain) and Tehran (chronic strain) of\n            <jats:italic>T. gondii,<\/jats:italic>\n            followed by treatment with EXO-ATQ. Their survival time and parasite load were compared with that in the suspension of ATQ (S-ATQ) as a positive control group. The\n            <jats:italic>in vitro<\/jats:italic>\n            study showed that exosomes improved the efficacy of ATQ, and EXO-ATQ significantly reduced intracellular proliferation of\n            <jats:italic>T. gondii<\/jats:italic>\n            tachyzoites compared to S-ATQ (\n            <jats:italic>P<\/jats:italic>\n            \u202f\u2264\u202f 0.05). In acute experimental toxoplasmosis, the mice treated with EXO-ATQ showed a significant reduction in tachyzoites count of the peritoneal cavity and a longer survival time (\n            <jats:italic>P<\/jats:italic>\n            \u202f\u2264\u202f 0.05). Furthermore, EXO-ATQ administration significantly decreased the mean number (97.3% cyst reduction) and the average size of the brain cysts of chronically infected mice with\n            <jats:italic>T. gondii<\/jats:italic>\n            , Tehran strain (\n            <jats:italic>P<\/jats:italic>\n            \u202f\u2264\u202f 0.05). Besides, the decrease in cyst numbers was confirmed by the down-regulation of\n            <jats:italic>BAG1<\/jats:italic>\n            using a real-time PCR assay. Our results implied that exosomes have the potential to be used as an efficient drug delivery system, and the loading of ATQ into the exosomes ameliorates the effect of ATQ against\n            <jats:italic>T. gondii<\/jats:italic>\n            . This study suggests a new strategy for improving the effectiveness of ATQ against acute and chronic phases of\n            <jats:italic>T. gondii<\/jats:italic>\n            .\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              This study is the first of its kind that suggests exosomes as a nano-carrier loaded with atovaquone (ATQ), which could be considered as a new strategy for improving the effectiveness of ATQ against acute and chronic phases of\n              <jats:italic>Toxoplasma gondii<\/jats:italic>\n              .\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.03080-23","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T14:00:29Z","timestamp":1701180029000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Formulation and evaluation of atovaquone-loaded macrophage-derived exosomes against\n            <i>Toxoplasma gondii<\/i>\n            :\n            <i>in vitro<\/i>\n            and\n            <i>in vivo<\/i>\n            assessment"],"prefix":"10.1128","volume":"12","author":[{"given":"Fatemeh","family":"Goudarzi","sequence":"first","affiliation":[{"name":"Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences , Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vahid","family":"Jajarmi","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences , Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeedeh","family":"Shojaee","sequence":"additional","affiliation":[{"name":"Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences , Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Mohebali","sequence":"additional","affiliation":[{"name":"Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences , Tehran, Iran"},{"name":"Center for Research of Endemic Parasites of Iran (CREPI), Tehran University of Medical Sciences , Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1031-9862","authenticated-orcid":true,"given":"Hossein","family":"Keshavarz","sequence":"additional","affiliation":[{"name":"Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences , Tehran, Iran"},{"name":"Center for Research of Endemic Parasites of Iran (CREPI), Tehran University of Medical Sciences , Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2020.06.012"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1051\/parasite\/2013017"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.3347\/kjp.2012.50.2.99"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.18502\/ijpa.v17i4.11271"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cpcardiol.2020.100741"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S158736"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28108-y"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.36.2.326"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms9091960"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.2217\/nnm.13.61"},{"key":"e_1_3_4_12_2","first-page":"989","article-title":"Solid lipid nanoparticles of atovaquone based on 2(4) full-factorial design","volume":"14","author":"Mohtar N","year":"2015","unstructured":"Mohtar N , A K Khan N , Darwis Y . 2015. 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