{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T17:19:39Z","timestamp":1788369579150,"version":"build-2803163510"},"reference-count":42,"publisher":"American Chemical Society (ACS)","issue":"1","license":[{"start":{"date-parts":[[2016,11,2]],"date-time":"2016-11-02T00:00:00Z","timestamp":1478044800000},"content-version":"vor","delay-in-days":11,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["259014"],"award-info":[{"award-number":["259014"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["RBAP114AMK"],"award-info":[{"award-number":["RBAP114AMK"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003500","name":"Universit\u00e0 degli Studi di Padova","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100003500","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,1,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>One of the most daunting challenges of nanomedicine is the finding of appropriate targeting agents to deliver suitable payloads precisely to cells affected by malignancies. Even more complex is the ability to ensure that the nanosystems enter those cells. Here, we use 2 nm (metal core) gold nanoparticles to target human hepatocellular carcinoma (HepG2) cells stably transfected with the SERPINB3 (SB3) protein. The nanoparticles were coated with a 85:15 mixture of thiols featuring, respectively, a phosphoryl choline (to ensure water solubility and biocompatibility) and a 28-mer peptide corresponding to the amino acid sequence 21\u201347 of the hepatitis B virus-PreS1 protein (PreS1(21\u201347)). Conjugation of the peptide was performed via the maleimide\u2013thiol reaction in methanol, allowing the use of a limited amount of the targeting molecule. This is an efficient procedure also in the perspective of selecting libraries of new targeting agents. The rationale behind the selection of the peptide is that SB3, which is undetectable in normal hepatocytes, is overexpressed in hepatocellular carcinoma and in hepatoblastoma and has been proposed as a target of the hepatitis B virus (HBV). For the latter, the key recognition element is the PreS1(21\u201347) peptide, which is a fragment of one of the proteins composing the viral envelope. The ability of the conjugated nanoparticles to bind the target protein SB3, expressed in liver cancer cells, was investigated by surface plasmon resonance analysis and in vitro via cellular uptake analysis followed by atomic absorption analysis of digested samples. The results showed that the PreS1(21\u201347) peptide is a suitable targeting agent for cells overexpressing the SB3 protein. Even more important is the evidence that the gold nanoparticles are internalized by the cells. The comparison between the surface plasmon resonance analysis and the cellular uptake studies suggests that the presentation of the protein on the cell surface is critical for efficient recognition.<\/jats:p>","DOI":"10.1021\/acs.bioconjchem.6b00441","type":"journal-article","created":{"date-parts":[[2016,10,22]],"date-time":"2016-10-22T11:14:12Z","timestamp":1477134852000},"page":"222-229","source":"Crossref","is-referenced-by-count":30,"title":["Binding and Uptake into Human Hepatocellular Carcinoma\nCells of Peptide-Functionalized Gold Nanoparticles"],"prefix":"10.1021","volume":"28","author":[{"given":"Satadru","family":"Jha","sequence":"first","affiliation":[{"name":"Universita\u0300 di Padova , , via Marzolo 1 , , ,","place":["Padova, Italy, 35131"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Ramadori","sequence":"additional","affiliation":[{"name":"Universita\u0300 di Padova , , via Marzolo 1 , , ,","place":["Padova, Italy, 35131"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santina","family":"Quarta","sequence":"additional","affiliation":[{"name":"Univerista\u0300 di Padova , , via Giustiniani, 2 , ,","place":["Padova, Italy, 35128"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Biasiolo","sequence":"additional","affiliation":[{"name":"Univerista\u0300 di Padova , , via Giustiniani, 2 , ,","place":["Padova, Italy, 35128"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrica","family":"Fabris","sequence":"additional","affiliation":[{"name":"Universita\u0300 di Padova , , via Marzolo 1 , , ,","place":["Padova, Italy, 35131"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Baldan","sequence":"additional","affiliation":[{"name":"Universita\u0300 di Padova , , via Marzolo 1 , , ,","place":["Padova, Italy, 35131"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetano","family":"Guarino","sequence":"additional","affiliation":[{"name":"Universita\u0300 di Padova , , via Marzolo 1 , , ,","place":["Padova, Italy, 35131"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariagrazia","family":"Ruvoletto","sequence":"additional","affiliation":[{"name":"Univerista\u0300 di Padova , , via Giustiniani, 2 , ,","place":["Padova, Italy, 35128"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianmarco","family":"Villano","sequence":"additional","affiliation":[{"name":"Univerista\u0300 di Padova , , via Giustiniani, 2 , ,","place":["Padova, Italy, 35128"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"Turato","sequence":"additional","affiliation":[{"name":"Univerista\u0300 di Padova , , via Giustiniani, 2 , ,","place":["Padova, Italy, 35128"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Gatta","sequence":"additional","affiliation":[{"name":"Univerista\u0300 di Padova , , via Giustiniani, 2 , ,","place":["Padova, Italy, 35128"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Mancin","sequence":"additional","affiliation":[{"name":"Universita\u0300 di Padova , , via Marzolo 1 , , ,","place":["Padova, Italy, 35131"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Pontisso","sequence":"additional","affiliation":[{"name":"Univerista\u0300 di Padova , , via Giustiniani, 2 , ,","place":["Padova, Italy, 35128"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Scrimin","sequence":"additional","affiliation":[{"name":"Universita\u0300 di Padova , , via Marzolo 1 , , ,","place":["Padova, Italy, 35131"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2016,10,22]]},"reference":[{"key":"2026090213095086900_cit1","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/0169-409X(95)00040-E","article-title":"Active targeting with particulate\ncarrier systems in the blood","volume":"17","author":"Crommelin","year":"1995","journal-title":"Adv. Drug Delivery\nRev."},{"key":"2026090213095086900_cit2","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1038\/nrc1566","article-title":"Cancer nanotechnology:\nopportunities and challenges","volume":"5","author":"Ferrari","year":"2005","journal-title":"Nat. Rev. Cancer"},{"key":"2026090213095086900_cit3","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1038\/nrd2591","article-title":"Strategies in the design\nof nanoparticles for therapeutic\napplications","volume":"9","author":"Petros","year":"2010","journal-title":"Nat. Rev. Drug Discovery"},{"key":"2026090213095086900_cit4","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1021\/ar200077p","article-title":"Multistage\nnanovectors: from concept to novel imaging contrast agents and therapeutics","volume":"44","author":"Godin","year":"2011","journal-title":"Acc. Chem. 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Pharm.\nBiopharm."},{"key":"2026090213095086900_cit8","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1016\/j.drudis.2006.07.005","article-title":"Exploiting the enhanced\npermeability and retention effect for tumor targeting","volume":"11","author":"Iyer","year":"2006","journal-title":"Drug Discovery Today"},{"key":"2026090213095086900_cit9","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1038\/nbt1340","article-title":"Renal clearance\nof quantum dots","volume":"25","author":"Choi","year":"2007","journal-title":"Nat. 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Evolution,\nmechanism of inhibition, novel functions and a revised nomenclature","volume":"276","author":"Silverman","year":"2001","journal-title":"J. Biol. Chem."},{"key":"2026090213095086900_cit15","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1038\/sj.bjc.6601543","article-title":"Overexpression of squamous cell carcinoma antigen variants\nin hepatocellular carcinoma","volume":"90","author":"Pontisso","year":"2004","journal-title":"Br. J. Cancer"},{"key":"2026090213095086900_cit16","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1136\/jcp.2007.051383","article-title":"Squamous cell\ncarcinoma antigen in human liver carcinogenesis","volume":"61","author":"Guido","year":"2008","journal-title":"J. Clin. 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Chem."},{"key":"2026090213095086900_cit20","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1128\/jvi.63.5.1981-1988.1989","article-title":"Human liver plasma\nmembranes contain receptors for the hepatitis B virus Pre-S1 region\nand, via polymerized human serum albumin, for the Pre-S2 region","volume":"8","author":"Pontisso","year":"1989","journal-title":"J. Virol."},{"key":"2026090213095086900_cit21","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1099\/vir.0.19130-0","article-title":"Surface expression of squamous cell carcinoma antigen\n(SCCA) can be increased by the preS1(21\u201347) sequence of hepatitis\nB virus","volume":"85","author":"Ruvoletto","year":"2004","journal-title":"J. Gen. Virol."},{"key":"2026090213095086900_cit22","doi-asserted-by":"publisher","first-page":"46709","DOI":"10.1074\/jbc.M302842200","article-title":"Squamous\ncell carcinoma antigen 1-mediated binding\nof hepatitis B virus to hepatocytes does not involve the hepatic serpin\nclearance system","volume":"278","author":"Moore","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2026090213095086900_cit23","doi-asserted-by":"publisher","first-page":"5714","DOI":"10.1111\/j.1742-4658.2008.06698.x","article-title":"Expression\nof squamous cell carcinoma antigen-1 in liver enhances the uptake\nof hepatitis B virus envelope-derived bio-nanocapsules in transgenic\nrats","volume":"275","author":"Kasuya","year":"2008","journal-title":"FEBS J."},{"issue":"1 Suppl","key":"2026090213095086900_cit24","doi-asserted-by":"publisher","first-page":"S32","DOI":"10.1016\/j.jhep.2016.02.011","article-title":"Entry of hepatitis\nB and hepatitis D virus into hepatocytes: Basic\ninsights and clinical implications","volume":"64","author":"Li","year":"2016","journal-title":"J. Hepatol."},{"key":"2026090213095086900_cit25","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.cocis.2012.12.003","article-title":"Catalysis on gold-nanoparticle-passivating\nmonolayers","volume":"18","author":"Mancin","year":"2013","journal-title":"Curr. Opin. Colloid Interface Sci."},{"key":"2026090213095086900_cit26","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1080\/10610270412331328817","article-title":"Nanozymes:\nfunctional nanoparticle-based\ncatalysts","volume":"17","author":"Pasquato","year":"2005","journal-title":"Supramol. Chem."},{"key":"2026090213095086900_cit27","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1021\/ar3000647","article-title":"The role of surface\nfunctionality in determining nanoparticle cytotoxicity","volume":"46","author":"Kim","year":"2013","journal-title":"Acc. Chem. 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Soc."},{"key":"2026090213095086900_cit32","doi-asserted-by":"publisher","first-page":"1523","DOI":"10.1039\/C1CC14726A","article-title":"Mapping the nanoparticles coating\nmonolayer with NMR pseudo-contact shifts","volume":"48","author":"Guarino","year":"2012","journal-title":"Chem.\nCommun."},{"key":"2026090213095086900_cit33","doi-asserted-by":"publisher","first-page":"12357","DOI":"10.1021\/la302168g","article-title":"Improved\nmethodology for the preparation of water-soluble\nmaleimide-functionalized small gold nanoparticles","volume":"28","author":"Gobbo","year":"2012","journal-title":"Langmuir"},{"key":"2026090213095086900_cit34","doi-asserted-by":"publisher","first-page":"5508","DOI":"10.1021\/la300316j","article-title":"Preparation\nof water-soluble maleimide-functionalized 3 nm gold nanoparticles:\na new bioconjugation template","volume":"28","author":"Zhu","year":"2012","journal-title":"Langmuir"},{"key":"2026090213095086900_cit35","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1002\/smll.201000279","article-title":"Preparation\nof stable maleimide-functionalized Au nanoparticles\nand their use in counting surface ligands","volume":"6","author":"Oh","year":"2010","journal-title":"Small"},{"key":"2026090213095086900_cit36","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1002\/rmv.376","article-title":"Interaction\nof hepatitis B virus\nwith cells","volume":"13","author":"Paran","year":"2003","journal-title":"Rev. Med. Virol."},{"key":"2026090213095086900_cit37","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1002\/jmv.23916","article-title":"Recent insights\ninto hepatitis B\nvirus\u2013host interactions","volume":"86","author":"Ezzikouri","year":"2014","journal-title":"J. Med. Virol."},{"key":"2026090213095086900_cit38","doi-asserted-by":"publisher","first-page":"827","DOI":"10.2147\/IJN.S27803","article-title":"Ferritin light chain\nand squamous cell carcinoma antigen 1 are coreceptors for cellular\nattachment and entry of hepatitis B virus","volume":"7","author":"Hao","year":"2012","journal-title":"Int.\nJ. Nanomed."},{"key":"2026090213095086900_cit39","doi-asserted-by":"publisher","first-page":"16014","DOI":"10.1038\/natrevmats.2016.14","article-title":"Analysis\nof nanoparticle delivery\nto tumours","volume":"1","author":"Wilhelm","year":"2016","journal-title":"Nat. Rev. Mater."},{"key":"2026090213095086900_cit40","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.1021\/ja411969e","article-title":"Efficient phosphodiester\ncleaving\nnanozymes resulting from multivalency and local medium polarity control","volume":"136","author":"Diez-Castellnou","year":"2014","journal-title":"J. Am. Chem. Soc."},{"key":"2026090213095086900_cit41","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1038\/labinvest.2010.55","article-title":"SERPINB3 modulates TGF-beta expression in chronic\nliver disease","volume":"90","author":"Turato","year":"2010","journal-title":"Lab. Invest."},{"key":"2026090213095086900_cit42","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1002\/path.2708","article-title":"SERPINB3\ninduces epithelial-mesenchymal\ntransition","volume":"221","author":"Quarta","year":"2010","journal-title":"J. Pathol."}],"container-title":["Bioconjugate Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.bioconjchem.6b00441","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/bcches\/article-pdf\/28\/1\/222\/66938251\/acs.bioconjchem.6b00441.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/bcches\/article-pdf\/28\/1\/222\/66938251\/acs.bioconjchem.6b00441.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T17:09:57Z","timestamp":1788368997000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/bcches\/article\/28\/1\/222\/728806\/Binding-and-Uptake-into-Human-Hepatocellular"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10,22]]},"references-count":42,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,10,22]]},"published-print":{"date-parts":[[2017,1,18]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.bioconjchem.6b00441","relation":{},"ISSN":["1043-1802","1520-4812"],"issn-type":[{"value":"1043-1802","type":"print"},{"value":"1520-4812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10,22]]}}}