{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T10:48:31Z","timestamp":1792666111811,"version":"4.5.0"},"reference-count":39,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2020,10,31]],"date-time":"2020-10-31T00:00:00Z","timestamp":1604102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["#BNPP02, #NMPP014"],"award-info":[{"award-number":["#BNPP02, #NMPP014"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["#104-2314B400-008, #103-2320B400-018, and #109-2314B400-019."],"award-info":[{"award-number":["#104-2314B400-008, #103-2320B400-018, and #109-2314B400-019."]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Polyethylene glycol (PEG) coating of gold nanoparticles (AuNPs) improves AuNP distribution via blood circulation. The use of PEG-coated AuNPs was shown to result in acute injuries to the liver, kidney, and spleen, but long-term toxicity has not been well studied. In this study, we investigated reporter induction for up to 90 days in NF-\u03baB transgenic reporter mice following intravenous injection of PEG-coated AuNPs. The results of different doses (1 and 4 \u03bcg AuNPs per gram of body weight), particle sizes (13 nm and 30 nm), and PEG surfaces (methoxyl- or carboxymethyl-PEG 5 kDa) were compared. The data showed up to 7-fold NF-\u03baB reporter induction in mouse liver from 3 h to 7 d post PEG-AuNP injection compared to saline-injected control mice, and gradual reduction to a level similar to control by 90 days. Agglomerates of PEG-AuNPs were detected in liver Kupffer cells, but neither gross pathological abnormality in liver sections nor increased activity of liver enzymes were found at 90 days. Injection of PEG-AuNPs led to an increase in collagen in liver sections and elevated total serum cholesterol, although still within the normal range, suggesting that inflammation resulted in mild fibrosis and affected hepatic function. Administrating PEG-AuNPs inevitably results in nanoparticles entrapped in the liver; thus, further investigation is required to fully assess the long-term impacts by PEG-AuNPs on liver health.<\/jats:p>","DOI":"10.3390\/ijms21218158","type":"journal-article","created":{"date-parts":[[2020,10,31]],"date-time":"2020-10-31T21:39:56Z","timestamp":1604180396000},"page":"8158","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Assessment of Polyethylene Glycol-Coated Gold Nanoparticle Toxicity and Inflammation In Vivo Using NF-\u03baB Reporter Mice"],"prefix":"10.3390","volume":"21","author":[{"given":"Tzu-Yin","family":"Chen","sequence":"first","affiliation":[{"name":"Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-Ru","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan-Wen","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan"},{"name":"Institute of Population Health, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Yan","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Ting","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin-Ying","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3433-5971","authenticated-orcid":false,"given":"Jen-Kun","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Shi","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1371-5569","authenticated-orcid":false,"given":"Kurt Ming-Chao","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.taap.2008.12.023","article-title":"Acute toxicity and pharmacokinetics of 13 nm-sized PEG-coated gold nanoparticles","volume":"236","author":"Cho","year":"2009","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4124","DOI":"10.1166\/jnn.2014.8274","article-title":"Quantitative biokinetics and systemic translocation of various gold nanostructures are highly dependent on their size and shape","volume":"14","author":"Zhang","year":"2014","journal-title":"J. Nanosci. Nanotechnol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1016\/j.biomaterials.2007.12.037","article-title":"Particle size-dependent organ distribution of gold nanoparticles after intravenous administration","volume":"29","author":"Hagens","year":"2008","journal-title":"Biomaterials"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e1542","DOI":"10.1002\/wnan.1542","article-title":"Probing the biological obstacles of nanomedicine with gold nanoparticles","volume":"11","author":"Li","year":"2019","journal-title":"WIREs Nanomed. Nanobiotechnol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1021\/acs.bioconjchem.6b00224","article-title":"Functionalized, long-circulating, and ultrasmall gold nanocarriers for overcoming the barriers of low nanoparticle delivery efficiency and poor tumor penetration","volume":"28","author":"Lee","year":"2017","journal-title":"Bioconjug. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1517\/17425241003777010","article-title":"Gold nanoparticles: Opportunities and challenges in nanomedicine","volume":"7","author":"Arvizo","year":"2010","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5483","DOI":"10.1002\/anie.201511733","article-title":"Basic physicochemical properties of polyethylene glycol coated gold nanoparticles that determine their interaction with cells","volume":"55","author":"Yang","year":"2016","journal-title":"Angew. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2139","DOI":"10.1021\/ja2084338","article-title":"Nanoparticle size and surface chemistry determine serum protein adsorption and macrophage uptake","volume":"134","author":"Walkey","year":"2012","journal-title":"J. Am. Chem. Soc."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2000153","DOI":"10.1002\/smll.202000153","article-title":"All roads lead to the liver: Metal nanoparticles and their implications for liver health","volume":"16","author":"Boey","year":"2020","journal-title":"Small"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.taap.2010.02.013","article-title":"Size-dependent tissue kinetics of PEG-coated gold nanoparticles","volume":"245","author":"Cho","year":"2010","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"639","DOI":"10.2147\/IJN.S185574","article-title":"A comparison of poly-ethylene-glycol-coated and uncoated gold nanoparticle-mediated hepatotoxicity and oxidative stress in Sprague Dawley rats","volume":"14","author":"Patlolla","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1007\/s11671-009-9334-6","article-title":"Assessment of the in vivo toxicity of gold nanoparticles","volume":"4","author":"Chen","year":"2009","journal-title":"Nanoscale Res. Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1002\/smll.200900626","article-title":"In vivo quantum-dot toxicity assessment","volume":"6","author":"Hauck","year":"2010","journal-title":"Small"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1097\/01.tp.0000203808.84963.13","article-title":"A novel method of monitoring response to islet transplantation: Bioluminescent imaging of an NF-kB transgenic mouse model","volume":"81","author":"Roth","year":"2006","journal-title":"Transplantation"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/nm0298-245","article-title":"Bioluminescent indicators in living mammals","volume":"4","author":"Contag","year":"1998","journal-title":"Nat. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1513\/pats.200507-067DS","article-title":"Bioluminescence imaging","volume":"2","author":"Sadikot","year":"2005","journal-title":"Proc. Am. Thorac. Soc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.4049\/jimmunol.168.3.1441","article-title":"In vivo imaging of NF-kappa B activity","volume":"168","author":"Carlsen","year":"2002","journal-title":"J. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1164\/ajrccm.162.3.9906129","article-title":"Multiorgan nuclear factor kappa B activation in a transgenic mouse model of systemic inflammation","volume":"162","author":"Blackwell","year":"2000","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11143","DOI":"10.1038\/s41598-019-47641-3","article-title":"A Tri-fusion reporter mouse reveals tissue-specific FGF1B promoter activity in vivo","volume":"9","author":"Liu","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1021\/ac503260f","article-title":"Establishment of a trimodality analytical platform for tracing, imaging and quantification of gold nanoparticles in animals by radiotracer techniques","volume":"87","author":"Chen","year":"2015","journal-title":"Anal. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1021\/acs.jpcc.6b10044","article-title":"Monitoring the transient thermal infrared emission of gold nanoparticles upon photoexcitation with a step-scan fourier-transform spectrometer","volume":"121","author":"Liu","year":"2017","journal-title":"J. Phys. Chem. C"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"199","DOI":"10.2217\/nnm.11.125","article-title":"Tissue and cellular distribution of gold nanoparticles varies based on aggregation\/agglomeration status","volume":"7","author":"Keene","year":"2012","journal-title":"Nanomedicine"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s12989-017-0206-4","article-title":"Evaluating the potential of gold, silver, and silica nanoparticles to saturate mononuclear phagocytic system tissues under repeat dosing conditions","volume":"14","author":"Weaver","year":"2017","journal-title":"Part. Fibre Toxicol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"104624","DOI":"10.1016\/j.yrtph.2020.104624","article-title":"Opportunities for use of one species for longer-term toxicology testing during drug development: A cross-industry evaluation","volume":"113","author":"Prior","year":"2020","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_25","unstructured":"European Medicines Agency (2020, October 21). ICH M3 (R2) Non-Clinical Safety Studies for the Conduct of Human Clinical Trials for Pharmaceuticals. Available online: https:\/\/www.ema.europa.eu\/en\/ich-m3-r2-non-clinical-safety-studies-conduct-human-clinical-trials-pharmaceuticals."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1002\/smll.200800922","article-title":"Biodistribution of 1.4-and 18-nm gold particles in rats","volume":"4","author":"Kreyling","year":"2008","journal-title":"Small"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.ejpb.2010.12.029","article-title":"Particle size-dependent and surface charge-dependent biodistribution of gold nanoparticles after intravenous administration","volume":"77","author":"Hirn","year":"2011","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.cld.2016.02.006","article-title":"The pathology of alcoholic liver disease","volume":"20","author":"Alpert","year":"2016","journal-title":"Clin. Liver Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1016\/j.jhep.2019.02.012","article-title":"Role of liver sinusoidal endothelial cells in non-alcoholic fatty liver disease","volume":"70","author":"Hammoutene","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1055\/s-0039-1678727","article-title":"Novel targets in the immune microenvironment of the hepatic sinusoids for treating liver diseases","volume":"39","author":"Patten","year":"2019","journal-title":"Semin. Liver Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1016\/j.csbj.2019.07.021","article-title":"Hallmarks of aging in the liver","volume":"17","author":"Hunt","year":"2019","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.tox.2012.01.013","article-title":"Susceptibility to gold nanoparticle-induced hepatotoxicity is enhanced in a mouse model of nonalcoholic steatohepatitis","volume":"294","author":"Hwang","year":"2012","journal-title":"Toxicology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"9334","DOI":"10.1021\/acs.est.7b02752","article-title":"Oral exposure to silver nanoparticles or silver ions may aggravate fatty liver disease in overweight mice","volume":"51","author":"Jia","year":"2017","journal-title":"Environ. Sci. Technol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s12951-018-0338-1","article-title":"Gold nanoparticles improve metabolic profile of mice fed a high-fat diet","volume":"16","author":"Chen","year":"2018","journal-title":"J. Nanobiotechnol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s12951-018-0414-6","article-title":"Gold nanoparticles as cell regulators: Beneficial effects of gold nanoparticles on the metabolic profile of mice with pre-existing obesity","volume":"16","author":"Chen","year":"2018","journal-title":"J. Nanobiotechnol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Chen, H., Dorrigan, A., Saad, S., Hare, D.J., Cortie, M.B., and Valenzuela, S.M. (2013). In vivo study of spherical gold nanoparticles: Inflammatory effects and distribution in mice. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0058208"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.immuni.2006.05.003","article-title":"Aging and innate immunity","volume":"24","author":"Solana","year":"2006","journal-title":"Immunity"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1039\/df9511100055","article-title":"A study of the nucleation and growth processes in the synthesis of colloidal gold","volume":"11","author":"Turkevich","year":"1951","journal-title":"Discuss. Faraday Soc."},{"key":"ref_39","unstructured":"(2020, October 23). Chondrex, Sirius Red\/Fast Green Collagen Staining Kit. Available online: https:\/\/www.chondrex.com\/products\/sirius-red-fast-green-collagen-staining-kit."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/21\/8158\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:27:37Z","timestamp":1760178457000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/21\/8158"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,31]]},"references-count":39,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["ijms21218158"],"URL":"https:\/\/doi.org\/10.3390\/ijms21218158","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,31]]}}}