{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T19:54:11Z","timestamp":1790538851217,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T00:00:00Z","timestamp":1640131200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF21OC0066562"],"award-info":[{"award-number":["NNF21OC0066562"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The use of nanoparticles (NPs) to deliver small inhibiting microRNAs (miRNAs) has shown great promise for treating cancer. However, constructing a miRNA delivery system that targets brain cancers, such as glioblastoma multiforme (GBM), remains technically challenging due to the existence of the blood\u2010tumor barrier (BTB). In this work, a novel targeted antisense miRNA\u201021 oligonucleotide (ATMO\u201021) delivery system is developed for GBM treatment. Bradykinin ligand agonist\u2010decorated spermine\u2010modified acetalated dextran NPs (SpAcDex NPs) could temporarily open the BTB by activating G\u2010protein\u2010coupled receptors that are expressed in tumor blood vessels and tumor cells, which increase transportation to and accumulation in tumor sites. ATMO\u201021 achieves high loading in the SpAcDex NPs (over 90%) and undergoes gradual controlled release with the degradation of the NPs in acidic lysosomal compartments. This allows for cell apoptosis and inhibition of the expression of vascular endothelial growth factor by downregulating hypoxia\u2010inducible factor (HIF\u20101<jats:italic>\u03b1<\/jats:italic>) protein. An in vivo orthotopic U87MG glioma model confirms that the released ATMO\u201021 shows significant therapeutic efficacy in inhibiting tumor growth and angiogenesis, demonstrating that agonist\u2010modified SpAcDex NPs represent a promising strategy for GBM treatment combining targeted gene therapy and antiangiogenic therapy.<\/jats:p>","DOI":"10.1002\/advs.202103812","type":"journal-article","created":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T12:23:49Z","timestamp":1640175829000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Anti\u2010MicroRNA\u201021 Oligonucleotide Loaded Spermine\u2010Modified Acetalated Dextran Nanoparticles for B1 Receptor\u2010Targeted Gene Therapy and Antiangiogenesis Therapy"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0626-4344","authenticated-orcid":false,"given":"Tao","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Health Technology Technical University of Denmark  Kongens Lyngby DK\u20102800 Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wentao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Health Technology Technical University of Denmark  Kongens Lyngby DK\u20102800 Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4773-2888","authenticated-orcid":false,"given":"Mohsen","family":"Mohammadniaei","sequence":"additional","affiliation":[{"name":"Department of Health Technology Technical University of Denmark  Kongens Lyngby DK\u20102800 Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7062-1019","authenticated-orcid":false,"given":"Jon","family":"Ashley","sequence":"additional","affiliation":[{"name":"Department of Health Technology Technical University of Denmark  Kongens Lyngby DK\u20102800 Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7191-4198","authenticated-orcid":false,"given":"Ming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Health Technology Technical University of Denmark  Kongens Lyngby DK\u20102800 Denmark"},{"name":"Jiangsu Collaborative Innovation Center for Biomedical Functional Materials School of Chemistry and Materials Science Nanjing Normal University  Nanjing 210023 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ninglin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Jiangsu Collaborative Innovation Center for Biomedical Functional Materials School of Chemistry and Materials Science Nanjing Normal University  Nanjing 210023 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Shen","sequence":"additional","affiliation":[{"name":"Jiangsu Collaborative Innovation Center for Biomedical Functional Materials School of Chemistry and Materials Science Nanjing Normal University  Nanjing 210023 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0210-4730","authenticated-orcid":false,"given":"Yi","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Health Technology Technical University of Denmark  Kongens Lyngby DK\u20102800 Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12,22]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.12.6242"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2012.204"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1800"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11007-0"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/nn504905q"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2010.11.079"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-2354"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3006839"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-01-012369"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201705660"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-0137"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2008.24"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-020-0075-7"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.200801478"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201101899"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abd6740"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0TB01821J"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2019.11.009"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.5b00694"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7SC00732A"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2012.05.020"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.201903686"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/bc100542r"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja803947s"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0901592106"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/adtp.202000076"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1006\/mthe.2002.0633"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd725"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/nn5003375"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-0464"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12307-019-00229-x"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202008802"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-016-0510-y"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2020.05.006"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(64)90139-1"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/0142-9612(91)90049-G"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00505-8"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nnano.2017.57"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja510085s"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201707164"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.0c04468"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202004929"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(02)03167-0"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2012.05.008"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-17-3415"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2011.07.001"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202103812","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202103812","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202103812","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T13:43:14Z","timestamp":1759758194000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202103812"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,22]]},"references-count":46,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,2]]}},"alternative-id":["10.1002\/advs.202103812"],"URL":"https:\/\/doi.org\/10.1002\/advs.202103812","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,22]]},"assertion":[{"value":"2021-08-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2103812"}}