{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:44:33Z","timestamp":1787510673406,"version":"build-2736575974"},"reference-count":37,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,14]],"date-time":"2024-01-14T00:00:00Z","timestamp":1705190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2021YFA1201004"],"award-info":[{"award-number":["2021YFA1201004"]}]},{"name":"National Key Research and Development Program of China","award":["32171378"],"award-info":[{"award-number":["32171378"]}]},{"name":"National Key Research and Development Program of China","award":["KM202110005014"],"award-info":[{"award-number":["KM202110005014"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2021YFA1201004"],"award-info":[{"award-number":["2021YFA1201004"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32171378"],"award-info":[{"award-number":["32171378"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["KM202110005014"],"award-info":[{"award-number":["KM202110005014"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Scientific Research Project of Beijing Educational Committee","award":["2021YFA1201004"],"award-info":[{"award-number":["2021YFA1201004"]}]},{"name":"Scientific Research Project of Beijing Educational Committee","award":["32171378"],"award-info":[{"award-number":["32171378"]}]},{"name":"Scientific Research Project of Beijing Educational Committee","award":["KM202110005014"],"award-info":[{"award-number":["KM202110005014"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Peptide-protected gold nanoclusters (AuNCs), possessing exceptional biocompatibility and remarkable physicochemical properties, have demonstrated intrinsic pharmaceutical activity in immunomodulation, making them a highly attractive frontier in the field of nanomedicine exploration. Autoimmune hepatitis (AIH) is a serious autoimmune liver disease caused by the disruption of immune balance, for which effective treatment options are still lacking. In this study, we initially identified glutathione (GSH)-protected AuNCs as a promising nanodrug candidate for AIH alleviating in a Concanavalin A (Con A)-induced mice model. However, to enhance treatment efficiency, liver-targeted delivery needs to be improved. Therefore, human serum albumin (HSA)-encapsulated AuNCs were constructed to achieve enhanced liver targeting and more potent mitigation of Con A-induced elevations in plasma aspartate transaminase (AST), alanine transaminase (ALT), and liver injury in mice. In vivo and in vitro mechanism studies indicated that AuNCs could suppress the secretion of IFN-\u03b3 by Con A-stimulated T cells and subsequently inhibit the activation of the JAK2\/STAT1 pathway and eventual hepatocyte apoptosis induced by IFN-\u03b3. These actions ultimately protect the liver from immune cell infiltration and damage caused by Con A. These findings suggest that bio-protected AuNCs hold promise as nanodrugs for AIH therapy, with their liver targeting capabilities and therapeutic efficiency being further improved via rational surface ligand engineering.<\/jats:p>","DOI":"10.3390\/pharmaceutics16010110","type":"journal-article","created":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T04:03:26Z","timestamp":1705291406000},"page":"110","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Enhancing Liver Delivery of Gold Nanoclusters via Human Serum Albumin Encapsulation for Autoimmune Hepatitis Alleviation"],"prefix":"10.3390","volume":"16","author":[{"given":"Cong","family":"Meng","sequence":"first","affiliation":[{"name":"Center of Excellence for Environmental Safety and Biological Effects, Beijing Key Laboratory for Green Catalysis and Separation, Department of Chemistry, Beijing University of Technology, Beijing 100124, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Biological and Chemical Engineering, Qilu Institute of Technology, Jinan 250200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuping","family":"Ming","sequence":"additional","affiliation":[{"name":"Center of Excellence for Environmental Safety and Biological Effects, Beijing Key Laboratory for Green Catalysis and Separation, Department of Chemistry, Beijing University of Technology, Beijing 100124, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cao","family":"Lu","sequence":"additional","affiliation":[{"name":"Center of Excellence for Environmental Safety and Biological Effects, Beijing Key Laboratory for Green Catalysis and Separation, Department of Chemistry, Beijing University of Technology, Beijing 100124, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanggege","family":"Li","sequence":"additional","affiliation":[{"name":"Center of Excellence for Environmental Safety and Biological Effects, Beijing Key Laboratory for Green Catalysis and Separation, Department of Chemistry, Beijing University of Technology, Beijing 100124, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center of Excellence for Environmental Safety and Biological Effects, Beijing Key Laboratory for Green Catalysis and Separation, Department of Chemistry, Beijing University of Technology, Beijing 100124, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongdong","family":"Su","sequence":"additional","affiliation":[{"name":"Center of Excellence for Environmental Safety and Biological Effects, Beijing Key Laboratory for Green Catalysis and Separation, Department of Chemistry, Beijing University of Technology, Beijing 100124, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyun","family":"Gao","sequence":"additional","affiliation":[{"name":"Center of Excellence for Environmental Safety and Biological Effects, Beijing Key Laboratory for Green Catalysis and Separation, Department of Chemistry, Beijing University of Technology, Beijing 100124, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4058-5931","authenticated-orcid":false,"given":"Qing","family":"Yuan","sequence":"additional","affiliation":[{"name":"Center of Excellence for Environmental Safety and Biological Effects, Beijing Key Laboratory for Green Catalysis and Separation, Department of Chemistry, Beijing University of Technology, Beijing 100124, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e070201","DOI":"10.1136\/bmj-2022-070201","article-title":"Diagnosis and Management of Autoimmune Hepatitis","volume":"380","author":"Muratori","year":"2023","journal-title":"BMJ"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6030","DOI":"10.3748\/wjg.v23.i33.6030","article-title":"Autoimmune Hepatitis: Standard Treatment and Systematic Review of Alternative Treatments","volume":"23","author":"Vergani","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"18017","DOI":"10.1038\/nrdp.2018.17","article-title":"Autoimmune Hepatitis","volume":"4","author":"Vergani","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1177\/2050640619872408","article-title":"Clinical Management of Autoimmune Hepatitis","volume":"7","author":"Pape","year":"2019","journal-title":"United Eur. Gastroenterol. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1016\/j.lpm.2017.08.012","article-title":"Autoimmune Hepatitis: Immunological Diagnosis","volume":"46","author":"Brahim","year":"2017","journal-title":"Presse Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1172\/JCI115836","article-title":"A T Cell-Dependent Experimental Liver Injury in Mice Inducible by Concanavalin A","volume":"90","author":"Tiegs","year":"1992","journal-title":"J. Clin. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"9437043","DOI":"10.1155\/2019\/9437043","article-title":"Autoimmune Hepatitis\u2014Immunologically Triggered Liver Pathogenesis\u2014Diagnostic and Therapeutic Strategies","volume":"2019","author":"Sucher","year":"2019","journal-title":"J. Immunol. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"108411","DOI":"10.1016\/j.intimp.2021.108411","article-title":"Pathogenesis of Concanavalin a Induced Autoimmune Hepatitis in Mice","volume":"102","author":"Hao","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"119","DOI":"10.3748\/wjg.v18.i2.119","article-title":"Immune Mechanisms of Concanavalin a Model of Autoimmune Hepatitis","volume":"18","author":"Wang","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1006\/cyto.2002.1948","article-title":"Cytokine Expression in Three Mouse Models of Experimental Hepatitis","volume":"19","author":"Sass","year":"2002","journal-title":"Cytokine"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"\u015awierczek, A., Plutecka, H., \u015alusarczyk, M., Ch\u0142o\u0144-Rzepa, G., and Wyska, E. (2021). Pk\/Pd Modeling of the Pde7 Inhibitor\u2014Grms-55 in a Mouse Model of Autoimmune Hepatitis. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13050597"},{"key":"ref_12","first-page":"1277","article-title":"Hydrogen Sulfide, a Potential Novel Drug, Attenuates Concanavalin a-Induced Hepatitis","volume":"8","author":"Cheng","year":"2014","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1053\/gast.1996.v111.pm8690213","article-title":"Interferon Gamma Plays a Critical Role in T Cell-Dependent Liver Injury in Mice Initiated by Concanavalin A","volume":"111","author":"Kusters","year":"1996","journal-title":"Gastroenterology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.4049\/jimmunol.159.3.1418","article-title":"Suppression of Concanavalin a-Induced Hepatitis in Ifn-Gamma (-\/-) Mice, but Not in Tnf-Alpha (-\/-) Mice: Role for Ifn-Gamma in Activating Apoptosis of Hepatocytes","volume":"159","author":"Tagawa","year":"1997","journal-title":"J. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"631","DOI":"10.2147\/DDDT.S99420","article-title":"Epigallocatechin-3-Gallate Attenuates Apoptosis and Autophagy in Concanavalin a-Induced Hepatitis by Inhibiting Bnip3","volume":"10","author":"Li","year":"2016","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/s41392-023-01536-y","article-title":"Nanomedicine in Cancer Therapy","volume":"8","author":"Fan","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"11879","DOI":"10.1021\/jacs.3c02880","article-title":"Ultrasmall Coinage Metal Nanoclusters as Promising Theranostic Probes for Biomedical Applications","volume":"145","author":"Yang","year":"2023","journal-title":"J. Am. Chem. Soc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5051","DOI":"10.1039\/D3TB00651D","article-title":"Biomolecule-Protected Gold Nanoclusters: Synthesis and Biomedical Applications","volume":"11","author":"Hao","year":"2023","journal-title":"J. Mater. Chem. B"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.mattod.2020.10.027","article-title":"Protein-Protected Metal Nanoclusters as Diagnostic and Therapeutic Platforms for Biomedical Applications","volume":"66","author":"Zare","year":"2021","journal-title":"Mater. Today"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"12095","DOI":"10.1039\/C6NR02750D","article-title":"Peptide Protected Gold Clusters: Chemical Synthesis and Biomedical Applications","volume":"8","author":"Yuan","year":"2016","journal-title":"Nanoscale"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1801671","DOI":"10.1002\/advs.201801671","article-title":"Au Clusters Treat Rheumatoid Arthritis with Uniquely Reversing Cartilage\/Bone Destruction","volume":"6","author":"Gao","year":"2019","journal-title":"Adv. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"18421","DOI":"10.1021\/acsnano.3c06025","article-title":"Colon-Accumulated Gold Nanoclusters Alleviate Intestinal Inflammation and Prevent Secondary Colorectal Carcinogenesis Via Nrf2-Dependent Macrophage Reprogramming","volume":"17","author":"Lu","year":"2023","journal-title":"ACS Nano"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Liu, Y., Meng, C., Li, Y., Xia, D., Lu, C., Lai, J., Zhang, Y., Cao, K., Gao, X., and Yuan, Q. (2023). Peptide-Protected Gold Nanoclusters Efficiently Ameliorate Acute Contact Dermatitis and Psoriasis Via Repressing the Tnf-A\/Nf-\u039ab\/Il-17a Axis in Keratinocytes. Nanomaterials, 13.","DOI":"10.3390\/nano13040662"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.biomaterials.2018.03.048","article-title":"Cytokine Induced Killer Cells-Assisted Delivery of Chlorin E6 Mediated Self-Assembled Gold Nanoclusters to Tumors for Imaging and Immuno-Photodynamic Therapy","volume":"170","author":"Xia","year":"2018","journal-title":"Biomaterials"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.imlet.2008.10.001","article-title":"Tetrandrine Protects Mice from Concanavalin a-Induced Hepatitis through Inhibiting Nf-\u039ab Activation","volume":"121","author":"Feng","year":"2008","journal-title":"Immunol. Lett."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"115017","DOI":"10.1016\/j.ecoenv.2023.115017","article-title":"Cadmium Induced Immunosuppression through Tlr-I\u03bab\u03b1-Nf\u03bab Signaling by Promoting Autophagic Degradation","volume":"259","author":"Gu","year":"2023","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1177\/15353702221128573","article-title":"Cx3cr1 Deficiency Exacerbates Immune-Mediated Hepatitis by Increasing Nf-\u039ab-Mediated Cytokine Production in Macrophage and T Cell","volume":"248","author":"Ren","year":"2023","journal-title":"Exp. Biol. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2216","DOI":"10.1039\/C9TB02767J","article-title":"Gold Nanoclusters for Biomedical Applications: Toward in Vivo Studies","volume":"8","author":"Porret","year":"2020","journal-title":"J. Mater. Chem. B"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"10525","DOI":"10.1039\/c3nr03121g","article-title":"Structure\u2013Activity Relationships for Biodistribution, Pharmacokinetics, and Excretion of Atomically Precise Nanoclusters in a Murine Model","volume":"5","author":"Wong","year":"2013","journal-title":"Nanoscale"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2004381","DOI":"10.1002\/smll.202004381","article-title":"Ligand Design in Ligand-Protected Gold Nanoclusters","volume":"17","author":"Zhang","year":"2021","journal-title":"Small"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4628","DOI":"10.1016\/j.biomaterials.2012.03.020","article-title":"In Vivo Renal Clearance, Biodistribution, Toxicity of Gold Nanoclusters","volume":"33","author":"Zhang","year":"2012","journal-title":"Biomaterials"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"16668","DOI":"10.1021\/acsnano.3c02877","article-title":"Encapsulation of an Antioxidant in Redox-Sensitive Self-Assembled Albumin Nanoparticles for the Treatment of Hepatitis","volume":"17","author":"Yasuda","year":"2023","journal-title":"ACS Nano"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4156","DOI":"10.1002\/jcp.26223","article-title":"Involvement of the Nrf2\/Ho-1\/Co Axis and Therapeutic Intervention with the Co-Releasing Molecule Corm-A1, in a Murine Model of Autoimmune Hepatitis","volume":"233","author":"Mangano","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1021\/ja806804u","article-title":"Protein-Directed Synthesis of Highly Fluorescent Gold Nanoclusters","volume":"131","author":"Xie","year":"2009","journal-title":"J. Am. Chem. Soc."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4042","DOI":"10.7150\/thno.42218","article-title":"Gold Clusters Prevent Breast Cancer Bone Metastasis by Suppressing Tumor-Induced Osteoclastogenesis","volume":"10","author":"Zhang","year":"2020","journal-title":"Theranostics"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"672","DOI":"10.3109\/09637486.2015.1077788","article-title":"Immunomodulatory Potential of a Brewers\u2019 Spent Grain Protein Hydrolysate Incorporated into Low-Fat Milk Following in Vitro gastrointestinal Digestion","volume":"66","author":"Crowley","year":"2015","journal-title":"Int. J. Food Sci. Nutr."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"140","DOI":"10.3389\/fphar.2017.00140","article-title":"Sophocarpine Protects Mice from Cona-Induced Hepatitis Via Inhibition of the Ifn-Gamma\/Stat1 Pathway","volume":"8","author":"Sang","year":"2017","journal-title":"Front. Pharmacol."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/16\/1\/110\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:46:32Z","timestamp":1760103992000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/16\/1\/110"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,14]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["pharmaceutics16010110"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics16010110","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,14]]}}}