{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T17:54:35Z","timestamp":1791136475073,"version":"4.1.0"},"reference-count":45,"publisher":"Elsevier BV","issue":"21-22","license":[{"start":{"date-parts":[[2008,11,1]],"date-time":"2008-11-01T00:00:00Z","timestamp":1225497600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2008,11,1]],"date-time":"2008-11-01T00:00:00Z","timestamp":1225497600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["bmn.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Drug Discovery Today"],"published-print":{"date-parts":[[2008,11]]},"DOI":"10.1016\/j.drudis.2008.07.009","type":"journal-article","created":{"date-parts":[[2008,9,12]],"date-time":"2008-09-12T15:52:41Z","timestamp":1221234761000},"page":"1002-1009","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":20,"title":["Doxorubicin coupled to lactosaminated human albumin: a hepatocellular carcinoma targeted drug"],"prefix":"10.1016","volume":"13","author":[{"given":"Luigi","family":"Fiume","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Baglioni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Bolondi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Farina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Di Stefano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.drudis.2008.07.009_bib1","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1016\/S0140-6736(03)14964-1","article-title":"Hepatocellular carcinoma","volume":"362","author":"Llovet","year":"2003","journal-title":"Lancet"},{"key":"10.1016\/j.drudis.2008.07.009_bib2","first-page":"1","article-title":"Drug targeting in human cancer chemotherapy","volume":"Vol. 82","author":"Schneider","year":"1984"},{"key":"10.1016\/j.drudis.2008.07.009_bib3","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1002\/hep.1840100215","article-title":"Effect of galactose on interaction of N-(2-hydroxypropyl) metacrylamide copolymers with hepatoma cells in culture: preliminary applications to an anticancer agents, daunomycin","volume":"10","author":"O\u2019Hare","year":"1989","journal-title":"Hepatology"},{"key":"10.1016\/j.drudis.2008.07.009_bib4","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/S0006-2952(98)00359-1","article-title":"Inhibition of [3H]thymidine incorporation into DNA of rat regenerating liver by 2\u2032,2\u2032-difluorodeoxycytidine coupled to lactosaminated poly-l-lysine","volume":"57","author":"Di Stefano","year":"1999","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.drudis.2008.07.009_bib5","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0021-9258(18)99337-3","article-title":"Physical and chemical studies on ceruloplasmin. V. Metabolic studies on sialic acid-free ceruloplasmin in vivo","volume":"243","author":"Morell","year":"1968","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.drudis.2008.07.009_bib6","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1146\/annurev.bi.51.070182.002531","article-title":"Carbohydrate-specific receptors of the liver","volume":"51","author":"Ashwell","year":"1982","journal-title":"Annu. Rev. Biochem."},{"key":"10.1016\/j.drudis.2008.07.009_bib7","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/0014-5793(79)81247-8","article-title":"Enhanced inhibition of virus DNA synthesis in hepatocytes by trifluorothymidine coupled to asialofetuin","volume":"103","author":"Fiume","year":"1979","journal-title":"FEBS Lett."},{"key":"10.1016\/j.drudis.2008.07.009_bib8","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/0014-5793(81)80179-2","article-title":"Hepatocyte targeting of adenine-9-\u03b2-d-arabinofuranoside 5\u2032-monophosphate (ara-AMP) coupled to lactosaminated albumin","volume":"129","author":"Fiume","year":"1981","journal-title":"FEBS Lett."},{"key":"10.1016\/j.drudis.2008.07.009_bib9","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/sj.bjc.6690708","article-title":"The asialoglycoprotein receptor in human hepatocellular carcinomas: its expression on proliferating cells","volume":"81","author":"Trer\u00e8","year":"1999","journal-title":"Br. J. Cancer"},{"key":"10.1016\/j.drudis.2008.07.009_bib10","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1016\/S0021-9258(17)38039-0","article-title":"Effect of reductive lactosamination on the hepatic uptake of bovine pancreatic ribonuclease A dimer","volume":"253","author":"Wilson","year":"1978","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.drudis.2008.07.009_bib11","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1002\/hep.510230401","article-title":"Adenine arabinoside monophosphate coupled to lactosaminated albumin, administered for 4 weeks to patients with chronic type B hepatitis, decreased viremia without producing significant side effects","volume":"23","author":"Torrani Cerenzia","year":"1996","journal-title":"Hepatology"},{"key":"10.1016\/j.drudis.2008.07.009_bib12","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/S0168-8278(01)00018-6","article-title":"Efficacy and safety of L-HSA\u2013ara-AMP in chronic hepatitis B patients non responder to interferon therapy: a randomised clinical trial","volume":"34","author":"Zarski","year":"2001","journal-title":"J. Hepatol."},{"key":"10.1016\/j.drudis.2008.07.009_bib13","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1111\/j.1478-3231.2006.01289.x","article-title":"A conjugate of doxorubicin with lactosaminated albumin enhances the drug concentrations in all the forms of rat hepatocellular carcinomas, independently of their differentiation grade","volume":"26","author":"Di Stefano","year":"2006","journal-title":"Liver Int."},{"key":"10.1016\/j.drudis.2008.07.009_bib14","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1111\/j.1478-3231.2005.1118.x","article-title":"Enhanced uptake of lactosaminated human albumin by rat hepatocarcinomas: implications for an improved chemotherapy of primary liver tumors","volume":"25","author":"Di Stefano","year":"2005","journal-title":"Liver Int."},{"key":"10.1016\/j.drudis.2008.07.009_bib15","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/0003-9861(77)90261-2","article-title":"Proteins containing reductively aminated saccharides. Synthesis and chemical characterization","volume":"181","author":"Schwartz","year":"1977","journal-title":"Arch. Biochem. Biophys."},{"key":"10.1016\/j.drudis.2008.07.009_bib16","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1021\/bc00024a015","article-title":"(6-Maleimidocaproyl)hydrazone derivative of doxorubicin \u2013 a new derivative for the preparation of immunoconjugates of doxorubicin","volume":"4","author":"Willner","year":"1993","journal-title":"Bioconjug. Chem."},{"key":"10.1016\/j.drudis.2008.07.009_bib17","first-page":"6600","article-title":"Evaluation in vitro of adriamycin immunoconjugates synthesized using an acid-sensitive hydrazone linker","volume":"50","author":"Greenfield","year":"1990","journal-title":"Cancer Res."},{"key":"10.1016\/j.drudis.2008.07.009_bib18","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0168-3659(01)00281-4","article-title":"New HPMA copolymers containing doxorubicin bound via pH-sensitive linkage: synthesis and preliminary in vitro and in vivo biological properties","volume":"73","author":"Etrych","year":"2001","journal-title":"J. Control. Release"},{"key":"10.1016\/j.drudis.2008.07.009_bib19","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.ejps.2007.11.005","article-title":"Doxorubicin coupled to lactosaminated albumin: effect of heterogeneity in drug load on conjugate disposition and hepatocellular carcinoma uptake in rats","volume":"33","author":"Di Stefano","year":"2008","journal-title":"Eur. J. Pharm. Sci."},{"key":"10.1016\/j.drudis.2008.07.009_bib20","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1039\/b600666n","article-title":"Maleimide spacers as versatile linkers in the synthesis of bioconjugates of anthracyclines","volume":"23","author":"Le Sann","year":"2006","journal-title":"Nat. Prod. Rep."},{"issue":"14S","key":"10.1016\/j.drudis.2008.07.009_bib21","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1200\/jco.2004.22.90140.2125","article-title":"Phase I dose-escalation and pharmacokinetic (PK) study of a (6-maleimidocaproyl)hydrazone derivative of doxorubicin (DOXO-EMCH) in patients with advanced cancers","volume":"22","author":"Drevs","year":"2004","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.drudis.2008.07.009_bib22","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1200\/JCO.2002.20.6.1668","article-title":"Hepatic drug targeting: phase I evaluation of polymer-bound doxorubicin","volume":"20","author":"Seymour","year":"2002","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.drudis.2008.07.009_bib23","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/S0168-3659(02)00016-0","article-title":"Differences in the intracellular fate of free and polymer-bound doxorubicin","volume":"80","author":"Hovorka","year":"2002","journal-title":"J. Control. Release"},{"key":"10.1016\/j.drudis.2008.07.009_bib24","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.ejps.2004.09.005","article-title":"A novel method for coupling doxorubicin to lactosaminated human albumin by an acid sensitive hydrazone bond: synthesis, characterization and preliminary biological properties of the conjugate","volume":"23","author":"Di Stefano","year":"2004","journal-title":"Eur. J. Pharm. Sci."},{"key":"10.1016\/j.drudis.2008.07.009_bib25","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1126\/science.152.3718.83","article-title":"Liver carcinogenesis by diethylnitrosamine in the rat","volume":"152","author":"Rajewsky","year":"1966","journal-title":"Science"},{"key":"10.1016\/j.drudis.2008.07.009_bib26","first-page":"219","article-title":"Quantitative comparison of toxicity of anticancer agents in mouse, rat, hamster, dog, monkey, and man","volume":"50","author":"Freireich","year":"1966","journal-title":"Cancer Chemother. Rep."},{"key":"10.1016\/j.drudis.2008.07.009_bib27","doi-asserted-by":"crossref","DOI":"10.1016\/j.dld.2008.05.014","article-title":"Binding of the doxorubicin-lactosaminated human albumin conjugate to HCC cells is mediated by the drug moieties","author":"Baglioni","year":"2008","journal-title":"Dig. Liver Dis."},{"key":"10.1016\/j.drudis.2008.07.009_bib28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0005-2736(80)90145-5","article-title":"Evidence of a specific complex between adriamycin and negatively charged phospholipids","volume":"597","author":"Goomaghtigh","year":"1980","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.drudis.2008.07.009_bib29","first-page":"1571","article-title":"Comparison of the cytotoxic effect of the high- and low-molecular-weight anticancer agents on multidrug-resistance Chinese hamster ovary cells in vitro","volume":"50","author":"Miyamoto","year":"1990","journal-title":"Cancer Res."},{"key":"10.1016\/j.drudis.2008.07.009_bib30","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.jhep.2005.02.045","article-title":"Doxorubicin coupled to lactosaminated albumin inhibits the growth of hepatocellular carcinomas induced in rats by diethylnitrosamine","volume":"43","author":"Fiume","year":"2005","journal-title":"J. Hepatol."},{"key":"10.1016\/j.drudis.2008.07.009_bib31","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1089\/cdd.1987.4.145","article-title":"Conjugates of ara-AMP with lactosaminated albumin: a study on their immunogenicity in mouse and rat","volume":"4","author":"Fiume","year":"1987","journal-title":"Cancer Drug Deliv."},{"key":"10.1016\/j.drudis.2008.07.009_bib32","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.dld.2006.02.010","article-title":"Doxorubicin coupled to lactosaminated albumin: effects on rats with liver fibrosis and cirrhosis","volume":"38","author":"Di Stefano","year":"2006","journal-title":"Dig. Liver Dis."},{"key":"10.1016\/j.drudis.2008.07.009_bib33","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1111\/j.1478-3231.2004.0916.x","article-title":"Liver targeted doxorubicin: effects on regenerating rat hepatocytes","volume":"24","author":"Di Stefano","year":"2004","journal-title":"Liver Int."},{"key":"10.1016\/j.drudis.2008.07.009_bib34","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.dld.2007.10.008","article-title":"Efficacy of doxorubicin coupled to lactosaminated albumin on rat HCCs evaluated by ultrasound imaging","volume":"40","author":"Di Stefano","year":"2008","journal-title":"Dig. Liver Dis."},{"key":"10.1016\/j.drudis.2008.07.009_bib35","first-page":"713","article-title":"Anthracyclines: a review of general and special toxicity studies","volume":"7","author":"Mazu\u00e8","year":"1995","journal-title":"Int. J. Oncol."},{"key":"10.1016\/j.drudis.2008.07.009_bib36","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.ejps.2006.10.012","article-title":"Coupling of lactose molecules to the carrier protein hinders the spleen and bone marrow uptake of doxorubicin conjugated with human albumin","volume":"30","author":"Di Stefano","year":"2007","journal-title":"Eur. J. Pharm. Sci."},{"key":"10.1016\/j.drudis.2008.07.009_bib37","doi-asserted-by":"crossref","first-page":"5231","DOI":"10.1158\/0008-5472.CAN-05-0440","article-title":"Three-dimensional high-frequency ultrasound imaging for longitudinal evaluation of liver metastases in preclinical models","volume":"65","author":"Graham","year":"2005","journal-title":"Cancer Res."},{"key":"10.1016\/j.drudis.2008.07.009_bib38","first-page":"679","article-title":"Effect of host microenvironment on the microcirculation of human colon adenocarcinoma","volume":"151","author":"Fukumura","year":"1997","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.drudis.2008.07.009_bib39","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/0169-409X(94)90007-8","article-title":"Soluble polymers for lectin-mediate drug targeting","volume":"14","author":"Seymour","year":"1994","journal-title":"Adv. Drug Deliv."},{"key":"10.1016\/j.drudis.2008.07.009_bib40","doi-asserted-by":"crossref","first-page":"15","DOI":"10.2165\/00003495-199700544-00005","article-title":"Polyethylene glycol-coated (pegylated) lyposomal doxorubicin. Rationale for use in solid tumors","volume":"54","author":"Gabizon","year":"1997","journal-title":"Drugs"},{"key":"10.1016\/j.drudis.2008.07.009_bib41","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1124\/dmd.32.8.794","article-title":"The hepatic pharmacokinetics of doxorubicin and liposomal doxorubicin","volume":"32","author":"Hilmer","year":"2004","journal-title":"Drug Metab. Dispos."},{"key":"10.1016\/j.drudis.2008.07.009_bib42","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1007\/s00280-003-0583-2","article-title":"A phase II and pharmacokinetic study of pegylated liposomal doxorubicin in patients with advanced hepatocellular carcinoma","volume":"51","author":"Hong","year":"2003","journal-title":"Cancer Chemother. Pharmacol."},{"key":"10.1016\/j.drudis.2008.07.009_bib43","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/j.jhep.2004.12.035","article-title":"Increase of doxorubicin sensitivity by doxorubicin-loading into nanoparticles for hepatocellular carcinoma cells in vitro and in vivo","volume":"42","author":"Barraud","year":"2005","journal-title":"J. Hepatol."},{"key":"10.1016\/j.drudis.2008.07.009_bib44","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/0959-8049(94)90299-2","article-title":"Increased bone marrow toxicity of doxorubicin bound to nanoparticles","volume":"30A","author":"Gibaud","year":"1994","journal-title":"Eur. J. Cancer"},{"key":"10.1016\/j.drudis.2008.07.009_bib45","doi-asserted-by":"crossref","first-page":"251","DOI":"10.2165\/00003495-200868020-00007","article-title":"Sorafenib in hepatocellular carcinoma","volume":"68","author":"Simpson","year":"2008","journal-title":"Drugs"}],"container-title":["Drug Discovery Today"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1359644608002778?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1359644608002778?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T12:02:34Z","timestamp":1761220954000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1359644608002778"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,11]]},"references-count":45,"journal-issue":{"issue":"21-22","published-print":{"date-parts":[[2008,11]]}},"alternative-id":["S1359644608002778"],"URL":"https:\/\/doi.org\/10.1016\/j.drudis.2008.07.009","relation":{},"ISSN":["1359-6446"],"issn-type":[{"value":"1359-6446","type":"print"}],"subject":[],"published":{"date-parts":[[2008,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Doxorubicin coupled to lactosaminated human albumin: a hepatocellular carcinoma targeted drug","name":"articletitle","label":"Article Title"},{"value":"Drug Discovery Today","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.drudis.2008.07.009","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2008 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}