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Although several studies have demonstrated their potential toxic effects, the real nature of the correlation between NP properties and their interaction with biological targets is still far from being fully elucidated. Here, engineered TiO2 NPs with various geometries (bipyramids, plates, and rods) have been prepared, characterized and intravenously administered in healthy mice. Parameters such as biodistribution, accumulation, and toxicity have been assessed in the lungs and liver. Our data show that the organ accumulation of TiO2 NPs, measured by ICP-MS, is quite low, and this is only partially and transiently affected by the NP geometries. The long-lasting permanence is exclusively restricted to the lungs. Here, bipyramids and plates show a higher accumulation, and interestingly, rod-shaped NPs are the most toxic, leading to histopathological pulmonary alterations. In addition, they are also able to induce a transient increase in serum markers related to hepatocellular injury. These results indicate that rods, more than bipyramidal and spherical geometries, lead to a stronger and more severe biological effect. Overall, small physico-chemical differences can dramatically modify both accumulation and safety.<\/jats:p>","DOI":"10.3390\/nano13071174","type":"journal-article","created":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T01:38:36Z","timestamp":1679881116000},"page":"1174","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Variations in Biodistribution and Acute Response of Differently Shaped Titania Nanoparticles in Healthy Rodents"],"prefix":"10.3390","volume":"13","author":[{"given":"Martina B.","family":"Violatto","sequence":"first","affiliation":[{"name":"Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milano, 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Mario Negri IRCCS, Via Mario Negri 2, 20156 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ngoc Lan","family":"Tran","sequence":"additional","affiliation":[{"name":"Experimental Hepatology Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5242-7861","authenticated-orcid":false,"given":"Qian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Institute of Nano Biomedicine and Engineering, Shanghai Jiao Tong University, 800 Dongchuan RD, Shanghai 200240, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atif","family":"Masood","sequence":"additional","affiliation":[{"name":"Karachi Institute of Radiotherapy and Nuclear 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Nano Biomedicine and Engineering, Shanghai Jiao Tong University, 800 Dongchuan RD, Shanghai 200240, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1672-6650","authenticated-orcid":false,"given":"Wolfgang J.","family":"Parak","sequence":"additional","affiliation":[{"name":"Center for Hybrid Nanostructures (CHyN), Universit\u00e4t Hamburg, Luruper Chaussee 149, 22607 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9098-9873","authenticated-orcid":false,"given":"Mario","family":"Salmona","sequence":"additional","affiliation":[{"name":"Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3144-7986","authenticated-orcid":false,"given":"Neus 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