aa84617fc2b42df3e0c44aeca15b06b9 pmc_10045098.pdf 0ffc7f445e1c3bf96c7140d694df84fd10e8d912 pmc_10045098.pdf 4bfe01bf965fde402d4f7da99ab31cde66e03489b8a8376519cf69b10aca04bb pmc_10045098.pdf Title: Exploring the Long-Term Tissue Accumulation and Excretion of 3 nm Cerium Oxide Nanoparticles after Single Dose Administration Subject: Nanoparticle (NP) pharmacokinetics significantly differ from traditional small molecule principles. From this emerges the need to create new tools and concepts to harness their full potential and avoid unnecessary risks. Nanoparticle pharmacokinetics strongly depend on size, shape, surface functionalisation, and aggregation state, influencing their biodistribution, accumulation, transformations, and excretion profile, and hence their efficacy and safety. Today, while NP biodistribution and nanoceria biodistribution have been studied often at short times, their long-term accumulation and excretion have rarely been studied. In this work, 3 nm nanoceria at 5.7 mg/kg of body weight was intravenously administrated in a single dose to healthy mice. Biodistribution was measured in the liver, spleen, kidney, lung, brain, lymph nodes, ovary, bone marrow, urine, and faeces at different time points (1, 9, 30, and 100 days). Biodistribution and urinary and faecal excretion were also studied in rats placed in metabolic cages at shorter times. The similarity of results of different NPs in different models is shown as the heterogeneous nanoceria distribution in organs. After the expectable accumulation in the liver and spleen, the concentration of cerium decays exponentially, accounting for about a 50% excretion of cerium from the body in 100 days. Cerium ions, coming from NP dissolution, are most likely excreted via the urinary tract, and ceria nanoparticles accumulated in the liver are most likely excreted via the hepatobiliary route. In addition, nanoceria looks safe and does not damage the target organs. No weight loss or apathy was observed during the course of the experiments. Keywords: nanoparticle biodistribution; nanopharmacokinetics; nanoceria; NP long-term accumulation; NP excretion; NP dissolution; nanosafety Author: Lena M. Ernst, Laura Mondragón, Joana Ramis, Muriel F. Gustà, Tetyana Yudina, Eudald Casals, Neus G. Bastús, Guillermo Fernández-Varo, Gregori Casals, Wladimiro Jiménez and Victor Puntes Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Mar 21 07:59:10 2023 CET ModDate: Tue Mar 21 08:19:41 2023 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 20 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 4822788 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- GASNFM+VnURWPalladioL Type 1 Custom yes yes no 10 0 XLPGHB+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 OBMKSY+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 MALSVA+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 IUYWSY+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 KUDXZB+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 46 0 FXZRFW+CMSY10 Type 1 Builtin yes yes no 77 0 NJYTIE+EURM10 Type 1 Builtin yes yes no 81 0 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of the Effects of Protein Corona on Nanoceria Internalization and Intracellular Trafficking Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: CeO2NPs Adsorption by Human Hepatocyte Cancer Cells Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Nanoceria Synthesis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Nanoceria Conjugation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Nanoceria Characterization Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Children: Item: Title: Bacterial Endotoxin (LAL) Test Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Transmission Electron Microscopy (TEM) Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: UV-Visible Spectra Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Dynamic Light Scattering (DLS) and -Potential Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: X-ray Diffraction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: In Vivo Study Design Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Children: Item: Title: Long-Term Biodistribution in Healthy Mice Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Nanoceria Excretion in CCl4-Treated Rats Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Confocal Imaging of Nanoparticles in Mice Liver Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Organ Distribution of Fe3O4NPs in CCl4-Treated Rats Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Organ Biodistribution after Oral Administration in Healthy Rats Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: Cerium Content Determination Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Info: Title: Exploring the Long-Term Tissue Accumulation and Excretion of 3 nm Cerium Oxide Nanoparticles after Single Dose Administration Author: Lena M. Ernst, Laura Mondragón, Joana Ramis, Muriel F. Gustà, Tetyana Yudina, Eudald Casals, Neus G. Bastús, Guillermo Fernández-Varo, Gregori Casals, Wladimiro Jiménez and Victor Puntes Subject: Nanoparticle (NP) pharmacokinetics significantly differ from traditional small molecule principles. From this emerges the need to create new tools and concepts to harness their full potential and avoid unnecessary risks. Nanoparticle pharmacokinetics strongly depend on size, shape, surface functionalisation, and aggregation state, influencing their biodistribution, accumulation, transformations, and excretion profile, and hence their efficacy and safety. Today, while NP biodistribution and nanoceria biodistribution have been studied often at short times, their long-term accumulation and excretion have rarely been studied. In this work, 3 nm nanoceria at 5.7 mg/kg of body weight was intravenously administrated in a single dose to healthy mice. Biodistribution was measured in the liver, spleen, kidney, lung, brain, lymph nodes, ovary, bone marrow, urine, and faeces at different time points (1, 9, 30, and 100 days). Biodistribution and urinary and faecal excretion were also studied in rats placed in metabolic cages at shorter times. The similarity of results of different NPs in different models is shown as the heterogeneous nanoceria distribution in organs. After the expectable accumulation in the liver and spleen, the concentration of cerium decays exponentially, accounting for about a 50% excretion of cerium from the body in 100 days. Cerium ions, coming from NP dissolution, are most likely excreted via the urinary tract, and ceria nanoparticles accumulated in the liver are most likely excreted via the hepatobiliary route. In addition, nanoceria looks safe and does not damage the target organs. No weight loss or apathy was observed during the course of the experiments. 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