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This study investigated the dissolution behavior and colloid-forming potential of UO2 in cell culture media, and compared the cytotoxicity, inflammatory response, and intracellular fate with those from equivalent aqueous uranium (U(aq)) exposures in murine RAW264.7 macrophages and Mlg2908 lung fibroblasts in vitro. In cell culture media, UO2 exhibited low solubility and limited colloid formation (\u223c5% colloidal), whereas U(aq) showed a higher proportion of colloid species (\u223c21%). In cellular exposure studies, particulate UO2 was generally more toxic than U(aq) across all concentrations (12\u2013120 \u03bcg\/mL; 50\u2013500 \u03bcM) and exposure durations (6\u201348 h). A significant inflammatory response was observed only in macrophages exposed to 60 \u03bcg\/mL of UO2. Uranium was predominantly recovered in the intracellular fraction of cells exposed to UO2 (68\u201379% of added U), whereas U(aq) exposures remained largely extracellular (\u223c1% intracellular fraction of added U). TEM showed that UO2 particles were localized within membrane-bound vesicular structures. HR-TEM and elemental analyses showed that internalized UO2 particles largely retained their chemical integrity after 24 h. Overall, these findings demonstrate that particulate UO2 is more toxic than U(aq), and its toxicity in vitro reflects cell-type-specific responses and particle stability following internalization, underscoring the importance of U speciation and physico-chemical form in inhalation health risk assessment.<\/jats:p>","DOI":"10.1021\/acsomega.6c06055","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T13:02:04Z","timestamp":1790341324000},"page":"59601-59612","source":"Crossref","is-referenced-by-count":0,"title":["Toxicity, Cellular\nUptake, and Intracellular Fate\nof Particulate and Dissolved Uranium in Murine Lung-Relevant Cell\nModels"],"prefix":"10.1021","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2445-136X","authenticated-orcid":true,"given":"You Cheng","family":"Khng","sequence":"first","affiliation":[{"name":"The University of Helsinki , , ,","place":["Helsinki, Finland, 00560"]},{"name":"National University of Singapore , , ,","place":["Singapore, Singapore, 118415"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0510-9542","authenticated-orcid":true,"given":"Gianni F.","family":"Vettese","sequence":"additional","affiliation":[{"name":"The University of Helsinki , , ,","place":["Helsinki, Finland, 00560"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Utsunomiya","sequence":"additional","affiliation":[{"name":"National Taiwan University , , No. 1, Sec. 4, Roosevelt Road , ,","place":["Taipei, Taiwan, 106"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M.","family":"Psyrillou","sequence":"additional","affiliation":[{"name":"The University of Helsinki , , ,","place":["Helsinki, Finland, 00560"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ole Christian","family":"Lind","sequence":"additional","affiliation":[{"name":"Norwegian University of Life Sciences , , P.O. Box 5003, ,","place":["\u00c5s, Norway, NO-1432"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Malmberg","sequence":"additional","affiliation":[{"name":"Chalmers University of Technology , , ,","place":["Go\u0308teborg, Sweden, 412 96"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2956-4366","authenticated-orcid":true,"given":"Mirkka","family":"Sarparanta","sequence":"additional","affiliation":[{"name":"The University of Helsinki , , ,","place":["Helsinki, Finland, 00560"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2320-6330","authenticated-orcid":true,"given":"Gareth T. 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