{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T22:47:35Z","timestamp":1782859655248,"version":"3.54.5"},"reference-count":40,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Lundbeck Foundation","award":["NK, R215-2015-4190"],"award-info":[{"award-number":["NK, R215-2015-4190"]}]},{"name":"Lundbeck Foundation","award":["670261"],"award-info":[{"award-number":["670261"]}]},{"name":"Lundbeck Foundation","award":["668532"],"award-info":[{"award-number":["668532"]}]},{"name":"Lundbeck Foundation","award":["126"],"award-info":[{"award-number":["126"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation program","award":["NK, R215-2015-4190"],"award-info":[{"award-number":["NK, R215-2015-4190"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation program","award":["670261"],"award-info":[{"award-number":["670261"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation program","award":["668532"],"award-info":[{"award-number":["668532"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation program","award":["126"],"award-info":[{"award-number":["126"]}]},{"name":"Novo Nordisk Foundation, Innovation Fund Denmark, Danish Cancer Society, Arvid Nilsson Foundation, Neye Foundation, Research Foundation of Rigshospitalet, Danish National Research Foundation","award":["NK, R215-2015-4190"],"award-info":[{"award-number":["NK, R215-2015-4190"]}]},{"name":"Novo Nordisk Foundation, Innovation Fund Denmark, Danish Cancer Society, Arvid Nilsson Foundation, Neye Foundation, Research Foundation of Rigshospitalet, Danish National Research Foundation","award":["670261"],"award-info":[{"award-number":["670261"]}]},{"name":"Novo Nordisk Foundation, Innovation Fund Denmark, Danish Cancer Society, Arvid Nilsson Foundation, Neye Foundation, Research Foundation of Rigshospitalet, Danish National Research Foundation","award":["668532"],"award-info":[{"award-number":["668532"]}]},{"name":"Novo Nordisk Foundation, Innovation Fund Denmark, Danish Cancer Society, Arvid Nilsson Foundation, Neye Foundation, Research Foundation of Rigshospitalet, Danish National Research Foundation","award":["126"],"award-info":[{"award-number":["126"]}]},{"name":"Research Council of the Capital Region of Denmark, Danish Health Authority, John and Birthe Meyer Foundation, and Research Council for Independent Research","award":["NK, R215-2015-4190"],"award-info":[{"award-number":["NK, R215-2015-4190"]}]},{"name":"Research Council of the Capital Region of Denmark, Danish Health Authority, John and Birthe Meyer Foundation, and Research Council for Independent Research","award":["670261"],"award-info":[{"award-number":["670261"]}]},{"name":"Research Council of the Capital Region of Denmark, Danish Health Authority, John and Birthe Meyer Foundation, and Research Council for Independent Research","award":["668532"],"award-info":[{"award-number":["668532"]}]},{"name":"Research Council of the Capital Region of Denmark, Danish Health Authority, John and Birthe Meyer Foundation, and Research Council for Independent Research","award":["126"],"award-info":[{"award-number":["126"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Objectives: We investigated the in vivo biodistribution of vascular cell adhesion molecule-1 (VCAM-1)-targeting polystyrene nanoparticles (PS-NPs) labeled with Rhodamine B in a murine model of atherosclerosis. Methods: Targeted PS-NPs of varying sizes were first assessed for in vitro uptake in RAW264.7 cells. In vivo evaluation with VCAM-1-targeted nanoparticles (NP T) in C57 BL\/6NtaC mice was conducted, and organs were analyzed 1, 6, and 24 h post injection, ex vivo. Subsequently, both targeted (NP T) and non-targeted (NP NT) nanoparticles of 30, 60, and 120 nm were injected into Apolipoprotein E knock-out (ApoE KO) mice on a high-fat diet, with ex vivo organ analysis 24 h post injection. Results: Results showed that NP30 T and NP60 T accumulated primarily in the liver and kidney of B6 mice. In ApoE KO mice, biodistribution was largely unaffected by size and targeting, except for higher uptake of NP 120 NT and T in the lungs and spleen. All NP types, except NP60 NT, showed significantly higher signal in ApoE KO mouse aortas compared to saline controls, with no significant differences between NP groups. Conclusions: While nanoparticles accumulated significantly in ApoE KO mouse aortas compared to controls, size and targeting properties did not significantly affect biodistribution in major organs 24 h post injection.<\/jats:p>","DOI":"10.3390\/diagnostics15172140","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T06:08:37Z","timestamp":1756102117000},"page":"2140","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effect of Size and Targeting Agent on Biodistribution of Polystyrene Nanoparticles in Apolipoprotein E Knock-Out and Wild-Type Mice"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5933-2075","authenticated-orcid":false,"given":"Harshvardhan Ajay","family":"Khare","sequence":"first","affiliation":[{"name":"Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital\u2013Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark"},{"name":"Department of Health Technology, Danish Technical University, \u00d8rsteds Plads, Building 345C, DK-2800 Kgs. Lyngby, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salime","family":"Bazban-Shotorbani","sequence":"additional","affiliation":[{"name":"Department of Health Technology, Danish Technical University, \u00d8rsteds Plads, Building 345C, DK-2800 Kgs. Lyngby, Denmark"},{"name":"Department of Chemistry, Molecular Sciences Research Hub, Imperial College London, White City Campus, Wood Lane, London W12 0BZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7898-4546","authenticated-orcid":false,"given":"Tina","family":"Binderup","sequence":"additional","affiliation":[{"name":"Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital\u2013Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2706-5547","authenticated-orcid":false,"given":"Andreas","family":"Kjaer","sequence":"additional","affiliation":[{"name":"Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital\u2013Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazila","family":"Kamaly","sequence":"additional","affiliation":[{"name":"Department of Health Technology, Danish Technical University, \u00d8rsteds Plads, Building 345C, DK-2800 Kgs. Lyngby, Denmark"},{"name":"Department of Chemistry, Molecular Sciences Research Hub, Imperial College London, White City Campus, Wood Lane, London W12 0BZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1016\/j.cell.2022.04.004","article-title":"Atherosclerosis: Recent developments","volume":"185","author":"Lusis","year":"2022","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1161\/CIRCULATIONAHA.107.699579","article-title":"General cardiovascular risk profile for use in primary care: The Framingham Heart Study","volume":"117","author":"Vasan","year":"2008","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1038\/s41586-021-03392-8","article-title":"The changing landscape of atherosclerosis","volume":"592","author":"Libby","year":"2021","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/s41572-019-0106-z","article-title":"Atherosclerosis","volume":"5","author":"Libby","year":"2019","journal-title":"Nat. Rev. Dis. Primers."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Mauersberger, C., Hinterdobler, J., Schunkert, H., Kessler, T., and Sager, H.B. (2022). Where the Action Is\u2014Leukocyte Recruitment in Atherosclerosis. Front. Cardiovasc. Med., 8.","DOI":"10.3389\/fcvm.2021.813984"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1093\/cvr\/cvad130","article-title":"Targeting endothelial vascular cell adhesion molecule-1 in atherosclerosis: Drug discovery and development of vascular cell adhesion molecule-1\u2013directed novel therapeutics","volume":"119","author":"Pickett","year":"2023","journal-title":"Cardiovasc. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2292","DOI":"10.1161\/ATVBAHA.107.149179","article-title":"Vascular Adhesion Molecules in Atherosclerosis","volume":"27","author":"Galkina","year":"2007","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1172\/JCI11871","article-title":"A major role for VCAM-1, but not ICAM-1, in early atherosclerosis","volume":"107","author":"Cybulsky","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1161\/01.RES.85.2.199","article-title":"Patterns of Vascular Cell Adhesion Molecule-1 and Intercellular Adhesion Molecule-1 Expression in Rabbit and Mouse Atherosclerotic Lesions and at Sites Predisposed to Lesion Formation","volume":"85","author":"Iiyama","year":"1999","journal-title":"Circ. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2000196","DOI":"10.1002\/adtp.202000196","article-title":"VCAM-1-Targeted Gene Delivery Nanoparticles Localize to Inflamed Endothelial Cells and Atherosclerotic Plaques","volume":"4","author":"Distasio","year":"2021","journal-title":"Adv. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Thayse, K., Kindt, N., Laurent, S., and Carlier, S. (2020). VCAM-1 Target in Non-Invasive Imaging for the Detection of Atherosclerotic Plaques. Biology, 9.","DOI":"10.3390\/biology9110368"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"723","DOI":"10.2217\/nnm-2023-0282","article-title":"VCAM-1-Targeted Nanoparticles to Diagnose, Monitor and Treat Atherosclerosis","volume":"19","author":"Castro","year":"2024","journal-title":"Nanomedicine"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1161\/CIRCULATIONAHA.106.646380","article-title":"Noninvasive Vascular Cell Adhesion Molecule-1 Imaging Identifies Inflammatory Activation of Cells in Atherosclerosis","volume":"114","author":"Nahrendorf","year":"2006","journal-title":"Circulation"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1161\/ATVBAHA.116.306483","article-title":"Molecular Imaging of Atherothrombotic Diseases","volume":"37","author":"Wang","year":"2017","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_15","first-page":"129","article-title":"Nanoparticles in modern medicine: State of the art and future challenges","volume":"2","author":"Murthy","year":"2007","journal-title":"Int. J. Nanomed."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/s41569-021-00629-x","article-title":"Macrophage-targeted nanomedicine for the diagnosis and treatment of atherosclerosis","volume":"19","author":"Chen","year":"2022","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.3762\/bjnano.5.250","article-title":"Functionalized polystyrene nanoparticles as a platform for studying bio-nano interactions","volume":"5","author":"Loos","year":"2014","journal-title":"Beilstein J. Nanotechnol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4077","DOI":"10.1021\/acsanm.1c00397","article-title":"Effect of Nanoparticle Biophysicochemical Properties on Binding and Transport across Cardiovascular Endothelial Dysfunction Models","volume":"4","author":"Khare","year":"2021","journal-title":"ACS Appl. Nano Mater."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1172\/JCI13005","article-title":"VCAM-1 is critical in atherosclerosis","volume":"107","author":"Ley","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ma, Y., Malbon, C.C., Williams, D.L., and Thorngate, F.E. (2008). Altered Gene Expression in Early Atherosclerosis Is Blocked by Low Level Apolipoprotein E. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0002503"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1161\/01.RES.84.11.1237","article-title":"Direct Demonstration of P-Selectin\u2013 and VCAM-1\u2013Dependent Mononuclear Cell Rolling in Early Atherosclerotic Lesions of Apolipoprotein E\u2013Deficient Mice","volume":"84","author":"Ramos","year":"1999","journal-title":"Circ. Res."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Bailly, A.L., Correard, F., Popov, A., Tselikov, G., Chaspoul, F., Appay, R., Al-Kattan, A., Kabashin, A.V., Braguer, D., and Esteve, M.-A. (2019). In vivo evaluation of safety, biodistribution and pharmacokinetics of laser-synthesized gold nanoparticles. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-48748-3"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.jconrel.2016.01.020","article-title":"Nanoparticle\u2013liver interactions: Cellular uptake and hepatobiliary elimination","volume":"240","author":"Zhang","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"763","DOI":"10.4155\/tde-2017-0057","article-title":"Challenges in realizing selectivity for nanoparticle biodistribution and clearance: Lessons from gold nanoparticles","volume":"8","author":"Berlin","year":"2017","journal-title":"Ther. Deliv."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1021\/mp800049w","article-title":"Pharmacokinetics and Biodistribution of Nanoparticles","volume":"5","author":"Li","year":"2008","journal-title":"Mol. Pharm."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Wu, J. (2021). The Enhanced Permeability and Retention (EPR) Effect: The Significance of the Concept and Methods to Enhance Its Application. J. Pers. Med., 11.","DOI":"10.3390\/jpm11080771"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e1901223","DOI":"10.1002\/adhm.201901223","article-title":"Size-Dependent EPR Effect of Polymeric Nanoparticles on Tumor Targeting","volume":"9","author":"Kang","year":"2020","journal-title":"Adv. Healthc. Mater."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.jconrel.2018.06.002","article-title":"A minimal physiologically based pharmacokinetic model that predicts anti-PEG IgG-mediated clearance of PEGylated drugs in human and mouse","volume":"284","author":"McSweeney","year":"2018","journal-title":"J. Control. Release"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/s41573-020-0090-8","article-title":"Engineering precision nanoparticles for drug delivery","volume":"20","author":"Mitchell","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.addr.2010.04.009","article-title":"The EPR effect: Unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect","volume":"63","author":"Fang","year":"2011","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1111\/jphp.13098","article-title":"An overview of active and passive targeting strategies to improve the nanocarriers efficiency to tumour sites","volume":"71","author":"Attia","year":"2019","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4141","DOI":"10.2147\/IJN.S109494","article-title":"Multicomponent, peptide-targeted glycol chitosan nanoparticles containing ferrimagnetic iron oxide nanocubes for bladder cancer multimodal imaging","volume":"11","author":"Key","year":"2016","journal-title":"Int. J. Nanomed."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8885","DOI":"10.1021\/acsnano.5b02611","article-title":"Multifunctional Nanoparticles Facilitate Molecular Targeting and miRNA Delivery to Inhibit Atherosclerosis in ApoE\u2013\/\u2013 Mice","volume":"9","author":"Kheirolomoom","year":"2015","journal-title":"ACS Nano"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1002\/cnma.201600043","article-title":"Targeted Delivery of Anti-miR-712 by VCAM1-Binding Au Nanospheres for Atherosclerosis Therapy","volume":"2","author":"Sun","year":"2016","journal-title":"ChemNanoMat"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"171101","DOI":"10.1063\/5.0021854","article-title":"The role of tissue fluorescence in in vivo optical bioimaging","volume":"128","author":"Lifante","year":"2020","journal-title":"J. Appl. Phys."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4550","DOI":"10.1002\/bit.27933","article-title":"Autofluorescence of blood and its application in biomedical and clinical research","volume":"118","author":"Shrirao","year":"2021","journal-title":"Biotechnol. Bioeng."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1007\/s00418-008-0511-y","article-title":"Molecular imaging with nanoparticles: Giant roles for dwarf actors","volume":"130","author":"Debbage","year":"2008","journal-title":"Histochem. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2967\/jnumed.107.045799","article-title":"Optical imaging: Current applications and future directions","volume":"49","author":"Luker","year":"2008","journal-title":"J. Nucl. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1021\/mp100309y","article-title":"Multimodal Clinical Imaging To Longitudinally Assess a Nanomedical Anti-Inflammatory Treatment in Experimental Atherosclerosis","volume":"7","author":"Lobatto","year":"2010","journal-title":"Mol. Pharm."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"461","DOI":"10.2967\/jnumed.120.256982","article-title":"PET Tracing of Biodistribution for Orally Administered 64Cu-Labeled Polystyrene in Mice","volume":"63","author":"Im","year":"2022","journal-title":"J. Nucl. Med."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/17\/2140\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:35:27Z","timestamp":1760034927000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/17\/2140"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,25]]},"references-count":40,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["diagnostics15172140"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics15172140","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,25]]}}}