{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:03:19Z","timestamp":1790380999089,"version":"4.1.0"},"reference-count":46,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2006,1,1]],"date-time":"2006-01-01T00:00:00Z","timestamp":1136073600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2006,1,1]],"date-time":"2006-01-01T00:00:00Z","timestamp":1136073600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2016,10,7]],"date-time":"2016-10-07T00:00:00Z","timestamp":1475798400000},"content-version":"vor","delay-in-days":3932,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy"],"published-print":{"date-parts":[[2006,1]]},"DOI":"10.1016\/j.ymthe.2005.07.687","type":"journal-article","created":{"date-parts":[[2005,9,9]],"date-time":"2005-09-09T12:15:06Z","timestamp":1126268106000},"page":"135-141","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":107,"title":["Lysosomal enzyme delivery by ICAM-1-targeted nanocarriers bypassing glycosylation- and clathrin-dependent endocytosis"],"prefix":"10.1016","volume":"13","author":[{"given":"Silvia","family":"Muro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward H.","family":"Schuchman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir R.","family":"Muzykantov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ymthe.2005.07.687_bib1","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1098\/rstb.2003.1269","article-title":"Enzyme replacement therapy: conception, chaos and culmination","volume":"358","author":"Brady","year":"2003","journal-title":"Philos. Trans. R. Soc. London B Biol. Sci."},{"key":"10.1016\/j.ymthe.2005.07.687_bib2","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1038\/nrg963","article-title":"Enzyme replacement and enhancement therapies: lessons from lysosomal disorders","volume":"3","author":"Desnick","year":"2002","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.ymthe.2005.07.687_bib3","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1038\/nrm1423","article-title":"The cell biology of lysosomal storage disorders","volume":"5","author":"Futerman","year":"2004","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"10.1016\/j.ymthe.2005.07.687_bib4","doi-asserted-by":"crossref","first-page":"2026","DOI":"10.1073\/pnas.74.5.2026","article-title":"Phosphohexosyl components of a lysosomal enzyme are recognized by pinocytosis receptors on human fibroblasts","volume":"74","author":"Kaplan","year":"1977","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymthe.2005.07.687_bib5","first-page":"138","article-title":"Steps in the phosphorylation of the high mannose oligosaccharides of lysosomal enzymes","volume":"92","author":"Kornfeld","year":"1982","journal-title":"Ciba Found. Symp."},{"key":"10.1016\/j.ymthe.2005.07.687_bib6","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1083\/jcb.93.1.135","article-title":"Biosynthesis of lysosomal hydrolases: their synthesis in bound polysomes and the role of co- and post-translational processing in determining their subcellular distribution","volume":"93","author":"Rosenfeld","year":"1982","journal-title":"J. Cell Biol."},{"key":"10.1016\/j.ymthe.2005.07.687_bib7","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1016\/S0140-6736(96)04451-0","article-title":"Therapeutic delivery of proteins to macrophages: implications for treatment of Gaucher's disease","volume":"348","author":"Mistry","year":"1996","journal-title":"Lancet"},{"key":"10.1016\/j.ymthe.2005.07.687_bib8","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/0076-6879(87)49041-1","article-title":"Lectin-specific targeting of lysosomal enzymes to reticuloendothelial cells","volume":"149","author":"Murray","year":"1987","journal-title":"Methods Enzymol."},{"key":"10.1016\/j.ymthe.2005.07.687_bib9","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/0304-4165(81)90474-8","article-title":"Uptake and distribution of placental glucocerebrosidase in rat hepatic cells and effects of sequential deglycosylation","volume":"673","author":"Furbish","year":"1981","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.ymthe.2005.07.687_bib10","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1124\/jpet.103.060236","article-title":"Dexamethasone-mediated up-regulation of the mannose receptor improves the delivery of recombinant glucocerebrosidase to Gaucher macrophages","volume":"308","author":"Zhu","year":"2004","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"10.1016\/j.ymthe.2005.07.687_bib11","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/0092-8674(78)90102-2","article-title":"Human beta-glucuronidase: in vivo clearance and in vitro uptake by a glycoprotein recognition system on reticuloendothelial cells","volume":"15","author":"Achord","year":"1978","journal-title":"Cell"},{"key":"10.1016\/j.ymthe.2005.07.687_bib12","first-page":"77","article-title":"The uptake of enzymes into lysosomes: an overview","volume":"16","author":"Neufeld","year":"1980","journal-title":"Birth Defects Orig. Artic. Ser."},{"key":"10.1016\/j.ymthe.2005.07.687_bib13","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1096\/fasebj.1.6.3315809","article-title":"Trafficking of lysosomal enzymes","volume":"1","author":"Kornfeld","year":"1987","journal-title":"FASEB J."},{"key":"10.1016\/j.ymthe.2005.07.687_bib14","doi-asserted-by":"crossref","first-page":"43160","DOI":"10.1074\/jbc.M107778200","article-title":"Biodistribution, kinetics, and efficacy of highly phosphorylated and non-phosphorylated beta-glucuronidase in the murine model of mucopolysaccharidosis VII","volume":"276","author":"Sands","year":"2001","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ymthe.2005.07.687_bib15","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/S0167-4838(99)00069-2","article-title":"Characterization of human acid sphingomyelinase purified from the media of overexpressing Chinese hamster ovary cells","volume":"1432","author":"He","year":"1999","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.ymthe.2005.07.687_bib16","doi-asserted-by":"crossref","first-page":"3083","DOI":"10.1073\/pnas.0308728100","article-title":"Glycosylation-independent targeting enhances enzyme delivery to lysosomes and decreases storage in mucopolysaccharidosis type VII mice","volume":"101","author":"LeBowitz","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymthe.2005.07.687_bib17","doi-asserted-by":"crossref","first-page":"35037","DOI":"10.1074\/jbc.M402630200","article-title":"Lipoprotein receptor binding, cellular uptake, and lysosomal delivery of fusions between the receptor-associated protein (RAP) and alpha-l-iduronidase or acid alpha-glucosidase","volume":"279","author":"Prince","year":"2004","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ymthe.2005.07.687_bib18","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1074\/jbc.M309465200","article-title":"Mannose 6-phosphate receptor-mediated uptake is defective in acid sphingomyelinase-deficient macrophages: implications for Niemann\u2013Pick disease enzyme replacement therapy","volume":"279","author":"Dhami","year":"2004","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ymthe.2005.07.687_bib19","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1242\/jcs.00367","article-title":"A novel endocytic pathway induced by clustering endothelial ICAM-1 or PECAM-1","volume":"116","author":"Muro","year":"2003","journal-title":"J. Cell Sci."},{"key":"10.1016\/j.ymthe.2005.07.687_bib20","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.2174\/1381612054367274","article-title":"Targeting of antioxidants and anti-thrombotic drugs to endothelial cell adhesion molecules","volume":"11","author":"Muro","year":"2005","journal-title":"Curr. Pharm. Des."},{"key":"10.1016\/j.ymthe.2005.07.687_bib21","doi-asserted-by":"crossref","first-page":"C1339","DOI":"10.1152\/ajpcell.00099.2003","article-title":"Slow intracellular trafficking of catalase nanoparticles targeted to ICAM-1 protects endothelial cells from oxidative stress","volume":"285","author":"Muro","year":"2003","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"10.1016\/j.ymthe.2005.07.687_bib22","unstructured":"Muro, S. (in press). VCAM-1 and ICAM-1. In The Endothelium: A Comprehensive Reference (W. Aird, Ed.), Cambridge Univ. Press, New York."},{"key":"10.1016\/j.ymthe.2005.07.687_bib23","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1002\/1531-8249(200002)47:2<229::AID-ANA13>3.0.CO;2-T","article-title":"Profile of endothelial and leukocyte activation in Fabry patients","volume":"47","author":"DeGraba","year":"2000","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.ymthe.2005.07.687_bib24","series-title":"Biomedical Aspects of Drug Targeting","first-page":"129","article-title":"Targeting pulmonary endothelium","author":"Muzykantov","year":"2003"},{"key":"10.1016\/j.ymthe.2005.07.687_bib25","first-page":"L806","article-title":"Immunotargeting of catalase to ACE or ICAM-1 protects perfused rat lungs against oxidative stress","volume":"275","author":"Atochina","year":"1998","journal-title":"Am. J. Physiol."},{"key":"10.1016\/j.ymthe.2005.07.687_bib26","doi-asserted-by":"crossref","first-page":"3977","DOI":"10.1182\/blood-2002-09-2853","article-title":"ICAM-directed vascular immunotargeting of antithrombotic agents to the endothelial luminal surface","volume":"101","author":"Murciano","year":"2003","journal-title":"Blood"},{"key":"10.1016\/j.ymthe.2005.07.687_bib27","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/nbt806","article-title":"Immunotargeting of catalase to the pulmonary endothelium alleviates oxidative stress and reduces acute lung transplantation injury","volume":"21","author":"Kozower","year":"2003","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2005.07.687_bib28","doi-asserted-by":"crossref","first-page":"L283","DOI":"10.1152\/ajplung.00021.2003","article-title":"PECAM-directed delivery of catalase to endothelium protects against pulmonary vascular oxidative stress","volume":"285","author":"Christofidou-Solomidou","year":"2003","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"10.1016\/j.ymthe.2005.07.687_bib29","doi-asserted-by":"crossref","first-page":"7570","DOI":"10.1073\/pnas.92.16.7570","article-title":"Generation of targeted retroviral vectors by using single-chain variable fragment: an approach to in vivo gene delivery","volume":"92","author":"Somia","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymthe.2005.07.687_bib30","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1007\/BF01756186","article-title":"Immunotargeting of daunomycin to localized and metastatic human colon adenocarcinoma in athymic mice","volume":"35","author":"Hurwitz","year":"1992","journal-title":"Cancer Immunol. Immunother."},{"key":"10.1016\/j.ymthe.2005.07.687_bib31","doi-asserted-by":"crossref","first-page":"15895","DOI":"10.1073\/pnas.2631433100","article-title":"Leukocyte-inspired biodegradable particles that selectively and avidly adhere to inflamed endothelium in vitro and in vivo","volume":"100","author":"Sakhalkar","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymthe.2005.07.687_bib32","doi-asserted-by":"crossref","first-page":"883","DOI":"10.4049\/jimmunol.168.2.883","article-title":"Selective intracellular delivery of dexamethasone into activated endothelial cells using an E-selectin-directed immunoconjugate","volume":"168","author":"Everts","year":"2002","journal-title":"J. Immunol."},{"key":"10.1016\/j.ymthe.2005.07.687_bib33","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1182\/blood.V99.3.912","article-title":"Size-dependent intracellular immunotargeting of therapeutic cargoes into endothelial cells","volume":"99","author":"Wiewrodt","year":"2002","journal-title":"Blood"},{"key":"10.1016\/j.ymthe.2005.07.687_bib34","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1182\/blood-2004-05-1714","article-title":"ICAM-1 recycling in endothelial cells: a novel pathway for sustained intracellular delivery and prolonged effects of drugs","volume":"105","author":"Muro","year":"2005","journal-title":"Blood"},{"key":"10.1016\/j.ymthe.2005.07.687_bib35","doi-asserted-by":"crossref","first-page":"281","DOI":"10.2174\/1570161043385736","article-title":"Endothelial endocytic pathways: gates for vascular drug delivery","volume":"2","author":"Muro","year":"2004","journal-title":"Curr. Vasc. Pharm."},{"key":"10.1016\/j.ymthe.2005.07.687_bib36","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.jconrel.2004.10.017","article-title":"Polymer nanocarriers protecting active enzyme cargo against proteolysis","volume":"102","author":"Dziubla","year":"2005","journal-title":"J. Controlled Release"},{"key":"10.1016\/j.ymthe.2005.07.687_bib37","series-title":"Methods in Molecular Biology: Bioconjugation Protocols","first-page":"3","article-title":"Streptavidin\u2013biotin crosslinking of therapeutic enzymes with carrier antibodies: nanoconjugates for protection against endothelial oxidative stress","author":"Shuvaev","year":"2004"},{"key":"10.1016\/j.ymthe.2005.07.687_bib38","unstructured":"Dziubla, T., Muro, S., Muzykantov, V. R., Koval, M. (in press). Nanoscale antioxidant therapeutics. In Oxidative Stress, Disease and Cancer (K.K. Singh, Ed.), Imperial College Press, London."},{"key":"10.1016\/j.ymthe.2005.07.687_bib39","series-title":"Methods in Molecular Biology. Bioconjugation Protocols","first-page":"21","article-title":"Targeting of antioxidants and anti-thrombotic drugs to endothelial cell adhesion molecules","author":"Muro","year":"2004"},{"key":"10.1016\/j.ymthe.2005.07.687_bib40","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1515\/bchm3.1994.375.7.447","article-title":"The tricyclic antidepressant desipramine causes proteolytic degradation of lysosomal sphingomyelinase in human fibroblasts","volume":"375","author":"Hurwitz","year":"1994","journal-title":"Biol. Chem. Hoppe-Seyler"},{"key":"10.1016\/j.ymthe.2005.07.687_bib41","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S0014-5793(04)00033-X","article-title":"Interactions of acid sphingomyelinase and lipid bilayers in the presence of the tricyclic antidepressant desipramine","volume":"559","author":"Kolzer","year":"2004","journal-title":"FEBS Lett."},{"key":"10.1016\/j.ymthe.2005.07.687_bib42","doi-asserted-by":"crossref","first-page":"18250","DOI":"10.1074\/jbc.273.29.18250","article-title":"The cellular trafficking and zinc dependence of secretory and lysosomal sphingomyelinase","volume":"273","author":"Schissel","year":"1998","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ymthe.2005.07.687_bib43","doi-asserted-by":"crossref","first-page":"5183","DOI":"10.4049\/jimmunol.162.9.5183","article-title":"Signaling pathways activated by leukocyte function-associated Ag-1-dependent costimulation","volume":"162","author":"Ni","year":"1999","journal-title":"J. Immunol."},{"key":"10.1016\/j.ymthe.2005.07.687_bib44","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/j.addr.2003.10.043","article-title":"ICAM-1: targeted docking for exogenous as well as endogenous ligands","volume":"56","author":"Hopkins","year":"2004","journal-title":"Adv. Drug Delivery Rev."},{"key":"10.1016\/j.ymthe.2005.07.687_bib45","doi-asserted-by":"crossref","first-page":"6432","DOI":"10.1073\/pnas.94.12.6432","article-title":"Intercellular adhesion molecule 1 knockout abrogates radiation induced pulmonary inflammation","volume":"94","author":"Hallahan","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymthe.2005.07.687_bib46","doi-asserted-by":"crossref","first-page":"151","DOI":"10.2174\/1568010023344689","article-title":"Current and future therapeutic strategies to target inflammation in stroke","volume":"1","author":"Zhang","year":"2002","journal-title":"Curr. Drug Targets Inflamm. Allergy"}],"container-title":["Molecular Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001605014255?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001605014255?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T17:48:41Z","timestamp":1761500921000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1525001605014255"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,1]]},"references-count":46,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2006,1]]}},"alternative-id":["S1525001605014255"],"URL":"https:\/\/doi.org\/10.1016\/j.ymthe.2005.07.687","relation":{},"ISSN":["1525-0016"],"issn-type":[{"value":"1525-0016","type":"print"}],"subject":[],"published":{"date-parts":[[2006,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Lysosomal enzyme delivery by ICAM-1-targeted nanocarriers bypassing glycosylation- and clathrin-dependent endocytosis","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ymthe.2005.07.687","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2005 The American Society of Gene Therapy. Published by Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}