{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T01:28:21Z","timestamp":1792978101830,"version":"4.5.0"},"reference-count":35,"publisher":"Elsevier BV","issue":"21","license":[{"start":{"date-parts":[[2011,7,1]],"date-time":"2011-07-01T00:00:00Z","timestamp":1309478400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2011,7,1]],"date-time":"2011-07-01T00:00:00Z","timestamp":1309478400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2011,7,1]],"date-time":"2011-07-01T00:00:00Z","timestamp":1309478400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2011,7,1]],"date-time":"2011-07-01T00:00:00Z","timestamp":1309478400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2011,7,1]],"date-time":"2011-07-01T00:00:00Z","timestamp":1309478400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2011,7,1]],"date-time":"2011-07-01T00:00:00Z","timestamp":1309478400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2011,7,1]],"date-time":"2011-07-01T00:00:00Z","timestamp":1309478400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100003827","name":"Nemzeti Kutat\u00e1si \u00e9s Technol\u00f3giai Hivatal","doi-asserted-by":"publisher","award":["CARPA777"],"award-info":[{"award-number":["CARPA777"]}],"id":[{"id":"10.13039\/501100003827","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011103","name":"Sixth Framework Programme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011103","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011102","name":"Seventh Framework Programme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011102","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biomaterials"],"published-print":{"date-parts":[[2011,7]]},"DOI":"10.1016\/j.biomaterials.2011.03.035","type":"journal-article","created":{"date-parts":[[2011,5,21]],"date-time":"2011-05-21T03:15:31Z","timestamp":1305947731000},"page":"4936-4942","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":116,"title":["In vitro and in vivo complement activation and related anaphylactic effects associated with polyethylenimine and polyethylenimine-graft-poly(ethylene glycol) block copolymers"],"prefix":"10.1016","volume":"32","author":[{"given":"Olivia M.","family":"Merkel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf","family":"Urbanics","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Bed\u0151cs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zolt\u00e1n","family":"Rozsnyay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e1szl\u00f3","family":"Rosivall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikl\u00f3s","family":"Toth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kissel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janos","family":"Szebeni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"12","key":"10.1016\/j.biomaterials.2011.03.035_bib1","doi-asserted-by":"crossref","first-page":"4234","DOI":"10.4049\/jimmunol.146.12.4234","article-title":"The role of surface charge in the activation of the classical and alternative pathways of complement by liposomes","volume":"146","author":"Chonn","year":"1991","journal-title":"J\u00a0Immunol"},{"issue":"3","key":"10.1016\/j.biomaterials.2011.03.035_bib2","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1089\/hum.1998.9.3-315","article-title":"Effects of complement depletion on the pharmacokinetics and gene delivery mediated by cationic lipid-DNA complexes","volume":"9","author":"Barron","year":"1998","journal-title":"Hum Gene Ther"},{"issue":"12","key":"10.1016\/j.biomaterials.2011.03.035_bib3","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1089\/hum.1996.7.12-1437","article-title":"Activation of the complement system by synthetic DNA complexes: a potential barrier for intravenous gene delivery","volume":"7","author":"Plank","year":"1996","journal-title":"Hum Gene Ther"},{"issue":"8","key":"10.1016\/j.biomaterials.2011.03.035_bib4","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1002\/jgm.773","article-title":"Recent advances in rational gene transfer vector design based on poly(ethylene imine) and its derivatives","volume":"7","author":"Neu","year":"2005","journal-title":"J\u00a0Gene Med"},{"issue":"2\u20133","key":"10.1016\/j.biomaterials.2011.03.035_bib5","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.addr.2007.03.010","article-title":"Toxicogenomics of non-viral drug delivery systems for rnai: potential impact on sirna-mediated gene silencing activity and specificity","volume":"59","author":"Akhtar","year":"2007","journal-title":"Adv Drug Deliv Rev"},{"issue":"3","key":"10.1016\/j.biomaterials.2011.03.035_bib6","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1021\/mp900278x","article-title":"Toxicity pathway focused gene expression profiling of pei-based polymers for pulmonary applications","volume":"7","author":"Beyerle","year":"2010","journal-title":"Mol Pharm"},{"issue":"2","key":"10.1016\/j.biomaterials.2011.03.035_bib7","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.taap.2009.10.001","article-title":"Pegylation affects cytotoxicity and cell-compatibility of poly(ethylene imine) for lung application: structure-function relationships","volume":"242","author":"Beyerle","year":"2010","journal-title":"Toxicol Appl Pharmacol"},{"issue":"1\u20133","key":"10.1016\/j.biomaterials.2011.03.035_bib8","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.jconrel.2004.07.009","article-title":"Polymer genomics: shifting the gene and drug delivery paradigms","volume":"101","author":"Kabanov","year":"2005","journal-title":"J\u00a0Control Release"},{"issue":"9","key":"10.1016\/j.biomaterials.2011.03.035_bib9","doi-asserted-by":"crossref","first-page":"2388","DOI":"10.1016\/j.biomaterials.2010.11.081","article-title":"Polymer-related off-target effects in non-viral sirna delivery","volume":"32","author":"Merkel","year":"2011","journal-title":"Biomaterials"},{"issue":"4","key":"10.1016\/j.biomaterials.2011.03.035_bib10","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1021\/bc034160m","article-title":"Physicochemical and biological characterization of polyethylenimine-graft-poly(ethylene glycol) block copolymers as a delivery system for oligonucleotides and ribozymes","volume":"15","author":"Brus","year":"2004","journal-title":"Bioconjug Chem"},{"issue":"4","key":"10.1016\/j.biomaterials.2011.03.035_bib11","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.biomaterials.2007.10.005","article-title":"Complement activation on surfaces carrying amino groups","volume":"29","author":"Toda","year":"2008","journal-title":"Biomaterials"},{"issue":"2\u20133","key":"10.1016\/j.biomaterials.2011.03.035_bib12","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/0169-409X(95)00029-7","article-title":"Pharmacokinetics of long-circulating liposomes","volume":"16","author":"Allen","year":"1995","journal-title":"Adv Drug Deliv Rev"},{"issue":"1","key":"10.1016\/j.biomaterials.2011.03.035_bib13","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/0005-2736(91)90162-2","article-title":"Sterically stabilized liposomes: a hypothesis on the molecular origin of the extended circulation times","volume":"1070","author":"Lasic","year":"1991","journal-title":"Biochim Biophys Acta"},{"issue":"1","key":"10.1016\/j.biomaterials.2011.03.035_bib14","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/0005-2736(91)90337-8","article-title":"Influence of surface hydrophilicity of liposomes on their interaction with plasma protein and clearance from the circulation: studies with poly(ethylene glycol)-coated vesicles","volume":"1062","author":"Senior","year":"1991","journal-title":"Biochim Biophys Acta"},{"issue":"1","key":"10.1016\/j.biomaterials.2011.03.035_bib15","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/0005-2736(94)90003-5","article-title":"Poly(ethylene glycol) on the liposome surface: on the mechanism of polymer-coated liposome longevity","volume":"1195","author":"Torchilin","year":"1994","journal-title":"Biochim Biophys Acta"},{"issue":"3","key":"10.1016\/j.biomaterials.2011.03.035_bib16","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1016\/S0022-3565(24)35391-1","article-title":"Accelerated blood clearance and altered biodistribution of repeated injections of sterically stabilized liposomes","volume":"292","author":"Dams","year":"2000","journal-title":"J\u00a0Pharmacol Exp Ther"},{"issue":"3","key":"10.1016\/j.biomaterials.2011.03.035_bib17","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.jconrel.2006.08.001","article-title":"Spleen plays an important role in the induction of accelerated blood clearance of pegylated liposomes","volume":"115","author":"Ishida","year":"2006","journal-title":"J\u00a0Control Release"},{"issue":"1","key":"10.1016\/j.biomaterials.2011.03.035_bib18","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jconrel.2006.01.005","article-title":"Injection of pegylated liposomes in rats elicits peg-specific igm, which is responsible for rapid elimination of a second dose of pegylated liposomes","volume":"112","author":"Ishida","year":"2006","journal-title":"J\u00a0Control Release"},{"issue":"4","key":"10.1016\/j.biomaterials.2011.03.035_bib19","doi-asserted-by":"crossref","first-page":"467","DOI":"10.3109\/08982100009031112","article-title":"The role of complement activation in hypersensitivity to pegylated liposomal doxorubicin (doxil\u00ae)","volume":"10","author":"Szebeni","year":"2000","journal-title":"J\u00a0Liposome Res"},{"issue":"1\u20132","key":"10.1016\/j.biomaterials.2011.03.035_bib20","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1081\/LPR-120004790","article-title":"Role of complement actvation in hypersensitivity reactions to doxil and hynic peg liposomes: experimental and clinical studies","volume":"12","author":"Szebeni","year":"2002","journal-title":"J\u00a0Liposome Res"},{"issue":"18","key":"10.1016\/j.biomaterials.2011.03.035_bib21","doi-asserted-by":"crossref","first-page":"6867","DOI":"10.1021\/ma012060a","article-title":"Synthesis, characterization, and biocompatibility of polyethylenimine-graft-poly(ethylene glycol) block copolymers","volume":"35","author":"Petersen","year":"2002","journal-title":"Macromolecules"},{"issue":"4","key":"10.1016\/j.biomaterials.2011.03.035_bib22","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1093\/jnci\/90.4.300","article-title":"Complement activation by cremophor el as a possible contributor to hypersensitivity to paclitaxel: an in vitro study","volume":"90","author":"Szebeni","year":"1998","journal-title":"J\u00a0Natl Cancer Inst"},{"key":"10.1016\/j.biomaterials.2011.03.035_bib23","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/S0076-6879(03)73010-9","article-title":"The interaction of liposomes with the complement system: in vitro and in vivo assays","volume":"373","author":"Szebeni","year":"2003","journal-title":"Methods Enzymol"},{"issue":"2","key":"10.1016\/j.biomaterials.2011.03.035_bib24","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.jconrel.2009.05.016","volume":"138","author":"Merkel","year":"2009","journal-title":"J\u00a0Control Release"},{"issue":"4","key":"10.1016\/j.biomaterials.2011.03.035_bib25","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1021\/bc049743q","article-title":"Pegylation of poly(ethylene imine) affects stability of complexes with plasmid DNA under in vivo conditions in a dose-dependent manner after intravenous injection into mice","volume":"16","author":"Merdan","year":"2005","journal-title":"Bioconjug Chem"},{"issue":"10","key":"10.1016\/j.biomaterials.2011.03.035_bib26","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1002\/jgm.598","article-title":"Purification of polyethylenimine polyplexes highlights the role of free polycations in gene transfer","volume":"6","author":"Boeckle","year":"2004","journal-title":"J\u00a0Gene Med"},{"issue":"9","key":"10.1016\/j.biomaterials.2011.03.035_bib27","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1093\/annonc\/mdg374","article-title":"Complement activation following first exposure to pegylated liposomal doxorubicin (doxil(r)): possible role in hypersensitivity reactions","volume":"14","author":"Chanan-Khan","year":"2003","journal-title":"Ann Oncol"},{"issue":"4","key":"10.1016\/j.biomaterials.2011.03.035_bib28","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1021\/bc025529v","article-title":"Polyethylenimine-graft-poly(ethylene glycol) copolymers: influence of copolymer block structure on DNA complexation and biological activities as gene delivery system","volume":"13","author":"Petersen","year":"2002","journal-title":"Bioconjug Chem"},{"issue":"6","key":"10.1016\/j.biomaterials.2011.03.035_bib29","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1023\/A:1016152831963","article-title":"The structure of peg-modified poly(ethylene imines) influences biodistribution and pharmacokinetics of their complexes with nf-kappab decoy in mice","volume":"19","author":"Kunath","year":"2002","journal-title":"Pharm Res"},{"issue":"4","key":"10.1016\/j.biomaterials.2011.03.035_bib30","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1038\/sj.gt.3300900","article-title":"Pegylated DNA\/transferrin-pei complexes: reduced interaction with blood components, extended circulation in blood and potential for systemic gene delivery","volume":"6","author":"Ogris","year":"1999","journal-title":"Gene Ther"},{"issue":"4","key":"10.1016\/j.biomaterials.2011.03.035_bib31","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/S0733-8635(18)30449-2","article-title":"The complement system. Activation, modulation, and clinical relevance","volume":"8","author":"Lim","year":"1990","journal-title":"Dermatol Clin"},{"issue":"17","key":"10.1016\/j.biomaterials.2011.03.035_bib32","doi-asserted-by":"crossref","first-page":"2302","DOI":"10.1161\/01.CIR.99.17.2302","article-title":"Hemodynamic changes induced by liposomes and liposome-encapsulated hemoglobin in pigs: a model for pseudoallergic cardiopulmonary reactions to liposomes. Role of complement and inhibition by soluble cr1 and anti-c5a antibody","volume":"99","author":"Szebeni","year":"1999","journal-title":"Circulation"},{"issue":"3","key":"10.1016\/j.biomaterials.2011.03.035_bib33","doi-asserted-by":"crossref","first-page":"H1050","DOI":"10.1152\/ajpheart.00622.2005","article-title":"Complement activation-related cardiac anaphylaxis in pigs: role of c5a anaphylatoxin and adenosine in liposome-induced abnormalities in ecg and heart function","volume":"290","author":"Szebeni","year":"2006","journal-title":"Am J Physiol Heart Circ Physiol"},{"issue":"3","key":"10.1016\/j.biomaterials.2011.03.035_bib34","doi-asserted-by":"crossref","first-page":"H1319","DOI":"10.1152\/ajpheart.2000.279.3.H1319","article-title":"Liposome-induced pulmonary hypertension: properties and mechanism of a complement-mediated pseudoallergic reaction","volume":"279","author":"Szebeni","year":"2000","journal-title":"Am J Physiol Heart Circ Physiol"},{"issue":"4","key":"10.1016\/j.biomaterials.2011.03.035_bib35","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1021\/mp900107v","article-title":"Nonviral sirna delivery to the lung: investigation of peg-pei polyplexes and their in vivo performance","volume":"6","author":"Merkel","year":"2009","journal-title":"Mol Pharm"}],"container-title":["Biomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0142961211002912?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0142961211002912?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T15:29:27Z","timestamp":1758900567000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0142961211002912"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,7]]},"references-count":35,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2011,7]]}},"alternative-id":["S0142961211002912"],"URL":"https:\/\/doi.org\/10.1016\/j.biomaterials.2011.03.035","relation":{},"ISSN":["0142-9612"],"issn-type":[{"value":"0142-9612","type":"print"}],"subject":[],"published":{"date-parts":[[2011,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"In vitro and in vivo complement activation and related anaphylactic effects associated with polyethylenimine and polyethylenimine-graft-poly(ethylene glycol) block copolymers","name":"articletitle","label":"Article Title"},{"value":"Biomaterials","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.biomaterials.2011.03.035","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2011 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}