{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T09:21:16Z","timestamp":1790328076811,"version":"4.1.0"},"reference-count":70,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T00:00:00Z","timestamp":1630886400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007210","name":"RWTH Aachen University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007210","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["331065168"],"award-info":[{"award-number":["331065168"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009398","name":"Medizinische Fakult\u00e4t, RWTH Aachen University","doi-asserted-by":"publisher","award":["G:(DE\u201082)ZUK2\u2010SF\u2010OPSF352"],"award-info":[{"award-number":["G:(DE\u201082)ZUK2\u2010SF\u2010OPSF352"]}],"id":[{"id":"10.13039\/501100009398","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Healthcare Materials"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Despite profound advances in treatment approaches, gliomas remain associated with very poor prognoses. The residual cells after incomplete resection often migrate and proliferate giving a seed for highly resistant gliomas. The efficacy of chemotherapeutic drugs is often strongly limited by their poor selectivity and the blood brain barrier (BBB). Therefore, the development of therapeutic carrier systems for efficient transport across the BBB and selective delivery to tumor cells remains one of the most complex problems facing molecular medicine and nano\u2010biotechnology. To address this challenge, a stimuli sensitive nanogel is synthesized using pre\u2010polymer approach for the effective delivery of nano\u2010irradiation. The nanogels are cross\u2010linked via matrix metalloproteinase (MMP\u20102,9) substrate and armed with Auger electron emitting drug 5\u2010[<jats:sup>125<\/jats:sup>I]Iodo\u20104\u201d\u2010thio\u20102\u201d\u2010deoxyuridine ([<jats:sup>125<\/jats:sup>I]ITdU) which after release can be incorporated into the DNA of tumor cells. Functionalization with diphtheria toxin receptor ligand allows nanogel transcytosis across the BBB at tumor site. Functionalized nanogels efficiently and increasingly explore transcytosis via BBB co\u2010cultured with glioblastoma cells. The subsequent nanogel degradation correlates with up\u2010regulated MMP2\/9. Released [<jats:sup>125<\/jats:sup>I]ITdU follows the thymidine salvage pathway ending in its incorporation into the DNA of tumor cells. With this concept, a highly efficient strategy for intracellular delivery of radiopharmaceuticals across the challenging BBB is presented.<\/jats:p>","DOI":"10.1002\/adhm.202100812","type":"journal-article","created":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T02:46:57Z","timestamp":1630982817000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Protease Responsive Nanogels for Transcytosis across the Blood\u2212Brain Barrier and Intracellular Delivery of Radiopharmaceuticals to Brain Tumor Cells"],"prefix":"10.1002","volume":"10","author":[{"given":"Smriti","family":"Singh","sequence":"first","affiliation":[{"name":"DWI\u2013Leibniz Institute for Interactive Material Research RWTH Aachen University  Aachen 52074 Germany"},{"name":"Max Planck Institute for Medical Research  Jahnstra\u00dfe 29 Heidelberg 69120 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natascha","family":"Drude","sequence":"additional","affiliation":[{"name":"DWI\u2013Leibniz Institute for Interactive Material Research RWTH Aachen University  Aachen 52074 Germany"},{"name":"Department of Nuclear Medicine RWTH Aachen University  Aachen 52074 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Blank","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine RWTH Aachen University  Aachen 52074 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prachi Bharat","family":"Desai","sequence":"additional","affiliation":[{"name":"DWI\u2013Leibniz Institute for Interactive Material Research RWTH Aachen University  Aachen 52074 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiltrud","family":"K\u00f6nigs","sequence":"additional","affiliation":[{"name":"Pathology\u2013Department of Electron Microscopy RWTH Aachen University  Aachen 52074 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"R\u00fctten","sequence":"additional","affiliation":[{"name":"Pathology\u2013Department of Electron Microscopy RWTH Aachen University  Aachen 52074 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl\u2010Josef","family":"Langen","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine RWTH Aachen University  Aachen 52074 Germany"},{"name":"Institute of Neuroscience and Medicine Forschungszentrum J\u00fclich  J\u00fclich 52428 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"M\u00f6ller","sequence":"additional","affiliation":[{"name":"DWI\u2013Leibniz Institute for Interactive Material Research RWTH Aachen University  Aachen 52074 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix M.","family":"Mottaghy","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine RWTH Aachen University  Aachen 52074 Germany"},{"name":"Department of Radiology and Nuclear Medicine Maastricht University Medical Center  Maastricht 6229 HX The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5712-6881","authenticated-orcid":false,"given":"Agnieszka","family":"Morgenroth","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine RWTH Aachen University  Aachen 52074 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,9,6]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a020412"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.01.003"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2017.11.040"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.6b03517"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.7b00616"},{"key":"e_1_2_8_4_3","doi-asserted-by":"publisher","DOI":"10.1208\/s12249-015-0287-z"},{"key":"e_1_2_8_4_4","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202001343"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2015.21"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.15406\/jnmr.2017.05.00132"},{"key":"e_1_2_8_5_3","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-44022-4_50"},{"key":"e_1_2_8_5_4","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2016.10.031"},{"key":"e_1_2_8_5_5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2017.12.015"},{"key":"e_1_2_8_5_6","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201901486"},{"key":"e_1_2_8_5_7","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202001375"},{"key":"e_1_2_8_5_8","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201900543"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.41161"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2017.02.006"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2016.11.014"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7BM01012E"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ddtec.2016.07.009"},{"key":"e_1_2_8_9_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2016.08.025"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-010-9496-x"},{"key":"e_1_2_8_10_2","first-page":"332","volume":"2","author":"Robinson M.","year":"2015","journal-title":"Mol. Sci."},{"key":"e_1_2_8_10_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.msec.2017.02.056"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425240902806383"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.5b00446"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/028418602321028229"},{"key":"e_1_2_8_14_1","first-page":"4s","volume":"46","author":"Kassis A. I.","year":"2005","journal-title":"J. Nucl. Med."},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.2307\/3578051"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.2123"},{"key":"e_1_2_8_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nucmedbio.2011.02.018"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-0907"},{"key":"e_1_2_8_17_2","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.107.040337"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biomac.7b00629"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/pola.23595"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2010.06.061"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.201704093"},{"key":"e_1_2_8_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/marc.201200744"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004010050901"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.24.7260"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.5306\/wjco.v3.i5.67"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161206775201901"},{"key":"e_1_2_8_25_2","doi-asserted-by":"publisher","DOI":"10.1215\/15228517-2008-106"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20349"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.200801393"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1593\/neo.04535"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-13-0240"},{"key":"e_1_2_8_29_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201701157R"},{"key":"e_1_2_8_29_3","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-0907"},{"key":"e_1_2_8_29_4","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.2123"},{"key":"e_1_2_8_30_1","first-page":"1148","volume":"39","author":"Kassis A. I.","year":"1998","journal-title":"J. Nucl. Med."},{"key":"e_1_2_8_30_2","doi-asserted-by":"publisher","DOI":"10.3109\/02841869609104048"},{"key":"e_1_2_8_30_3","first-page":"5199","volume":"50","author":"Kassis A. I.","year":"1990","journal-title":"Cancer Res."},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/0305-0491(96)00033-8"},{"key":"e_1_2_8_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gng121"},{"key":"e_1_2_8_31_3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0058938"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.4205"},{"key":"e_1_2_8_33_1","first-page":"1218","volume":"43","author":"Toyohara J.","year":"2002","journal-title":"J. Nucl. Med."},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.09.162"},{"key":"e_1_2_8_34_2","doi-asserted-by":"publisher","DOI":"10.3390\/ph4121591"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2018.05.005"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-010-9471-5"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1080\/15384047.2018.1423924"},{"key":"e_1_2_8_37_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-2753"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.1113"},{"key":"e_1_2_8_38_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biomac.7b00629"},{"key":"e_1_2_8_38_3","doi-asserted-by":"publisher","DOI":"10.1002\/smll.201704093"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1840698"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01631814"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/2045-8118-10-33"}],"container-title":["Advanced Healthcare Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.202100812","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/adhm.202100812","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.202100812","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T15:39:45Z","timestamp":1759765185000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adhm.202100812"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,6]]},"references-count":70,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["10.1002\/adhm.202100812"],"URL":"https:\/\/doi.org\/10.1002\/adhm.202100812","archive":["Portico"],"relation":{},"ISSN":["2192-2640","2192-2659"],"issn-type":[{"value":"2192-2640","type":"print"},{"value":"2192-2659","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,6]]},"assertion":[{"value":"2021-04-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2100812"}}