{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:57:12Z","timestamp":1790618232377,"version":"4.1.0"},"reference-count":121,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>This review aimed to explore emerging therapeutic strategies for glioblastoma multiforme (GBM) through the integration of lactoferrin (LF) and nanotechnology, emphasizing mechanisms that improve drug delivery across the blood\u2013brain barrier (BBB).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Published studies on LF\u2010based nanocarriers and their biological mechanisms were systematically reviewed, focusing on LF's molecular interactions, tumor\u2010targeting capacity, and the design of nanoscale delivery systems capable of enhancing drug bioavailability and selectivity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>LF, an iron\u2010binding glycoprotein with antimicrobial, antioxidant, and antitumor properties, can interact with low\u2010density lipoprotein receptor\u2010related protein\u20101 (LRP1), enabling its transport across the BBB and preferential uptake by glioblastoma cells. Nanocarrier systems incorporating LF improved the solubility, circulation half\u2010life (typically 2\u2010 to 5\u2010fold enhancement compared with free drug), and therapeutic performance of chemotherapeutic agents while minimizing systemic toxicity. Studies demonstrated that LF\u2010based nanoparticles could induce apoptosis, inhibit tumor growth (with tumor volume reductions ranging from approximately 40% to 70% in orthotopic GBM models), and enhance radiosensitivity in GBM models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>LF provides a promising molecular platform for targeted glioblastoma therapy. When integrated with nanocarrier technologies, it enhances therapeutic efficacy, stability, and safety of anticancer agents. The combined LF\u2013nanocarrier approach represents a rational and innovative strategy for improving treatment outcomes in glioblastoma multiforme.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71070","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T06:30:41Z","timestamp":1789453841000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lactoferrin and Nanotechnology: New Insights Into Glioblastoma Therapy"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6408-5953","authenticated-orcid":false,"given":"Atena","family":"Abed","sequence":"first","affiliation":[{"name":"Department of Medical Biotechnology, School of Advanced Technologies Shahrekord University of Medical Sciences  Shahrekord Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2930-1213","authenticated-orcid":false,"given":"Javad Amini","family":"Mahabadi","sequence":"additional","affiliation":[{"name":"Anatomical Sciences Research Center, Institute for Basic Sciences Kashan University of Medical Sciences  Kashan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2015.05.005"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-022-02349-7"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2022.09.005"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-021-00752-y"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2023.114821"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.01.012"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-010814-124852"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.9b14046"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.4c02696"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202303073"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2015.17"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noz150"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A8368"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-026-05470-1"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics16030458"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noaa200"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21613"},{"issue":"9","key":"e_1_2_12_19_1","first-page":"2613","article-title":"Survival Analysis of Glioblastoma Multiforme","volume":"19","author":"Witthayanuwat S.","year":"2018","journal-title":"Asian Pacific Journal of Cancer Prevention"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noy002"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2018.00318"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-18-1733"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-75372-3"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics13071053"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26010205"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18091985"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2022.1018336"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom15081174"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jiac.2014.08.003"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00005-021-00637-2"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1088\/1748-605X\/ad6e47"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2024.02.020"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2024.216002"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.5c11173"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01438"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12123806"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00705"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20092128"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02123"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom10030456"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10534-022-00484-4"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2019.1650114"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-6-1"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-021-01769-z"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1139\/bcb-2020-0074"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-022-07943-8"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-023-04524-9"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425247.2018.1505858"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2023.147355"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2018.00200"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1080\/21691401.2020.1850465"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph192316193"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S347574"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.62.14.13"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12013-022-01097-x"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfb.2021.111694"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.52028"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.3c00052"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-015-1441-4"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-16962-6"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfb.2022.112657"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2022.09.120"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c01684"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2022.847573"},{"key":"e_1_2_12_65_1","first-page":"25","article-title":"Biodegradable Eri Silk Nanoparticles as a Delivery Vehicle for Bovine Lactoferrin Against MDA\u2010MB\u2010231 and MCF\u20107 Breast Cancer Cells","volume":"11","author":"Roy K.","year":"2016","journal-title":"International Journal of Nanomedicine"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S316830"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1139\/bcb-2016-0094"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/2187696"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep32062"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.201803703"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.0c00086"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.1139\/bcb-2020-0087"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2023.123163"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.3168\/jds.2009-2926"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12906-023-04045-1"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.9b01639"},{"key":"e_1_2_12_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfb.2020.110824"},{"key":"e_1_2_12_78_1","first-page":"4081","article-title":"Oral Administration of Iron\u2010Saturated Bovine Lactoferrin\u2013Loaded Ceramic Nanocapsules for Breast Cancer Therapy and Influence on Iron and Calcium Metabolism","volume":"10","author":"Mahidhara G.","year":"2015","journal-title":"International Journal of Nanomedicine"},{"key":"e_1_2_12_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2020.119097"},{"key":"e_1_2_12_80_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biomac.3c00037"},{"key":"e_1_2_12_81_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-36492-8"},{"key":"e_1_2_12_82_1","doi-asserted-by":"publisher","DOI":"10.3168\/jds.2010-3629"},{"key":"e_1_2_12_83_1","doi-asserted-by":"publisher","DOI":"10.3390\/foods12142662"},{"key":"e_1_2_12_84_1","doi-asserted-by":"publisher","DOI":"10.2217\/nnm.15.199"},{"issue":"5","key":"e_1_2_12_85_1","first-page":"5688","article-title":"Inhibition of DMH\u2010DSS\u2010Induced Colorectal Cancer by Liposomal Bovine Lactoferrin in Rats","volume":"14","author":"Sugihara Y.","year":"2017","journal-title":"Oncology Letters"},{"key":"e_1_2_12_86_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.11394"},{"key":"e_1_2_12_87_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b23-00011"},{"key":"e_1_2_12_88_1","doi-asserted-by":"publisher","DOI":"10.2217\/nnm-2018-0196"},{"key":"e_1_2_12_89_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-43725-3"},{"key":"e_1_2_12_90_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.129466"},{"key":"e_1_2_12_91_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24071195"},{"key":"e_1_2_12_92_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01221"},{"key":"e_1_2_12_93_1","doi-asserted-by":"publisher","DOI":"10.2217\/nnm-2020-0090"},{"key":"e_1_2_12_94_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40824-023-00391-w"},{"key":"e_1_2_12_95_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2019.109461"},{"key":"e_1_2_12_96_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2023.02.002"},{"key":"e_1_2_12_97_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.8b01056"},{"key":"e_1_2_12_98_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-020-00751-x"},{"key":"e_1_2_12_99_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.3c00239"},{"key":"e_1_2_12_100_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1NR03553C"},{"key":"e_1_2_12_101_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11671-016-1421-x"},{"key":"e_1_2_12_102_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-021-01180-0"},{"key":"e_1_2_12_103_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-06888-4"},{"key":"e_1_2_12_104_1","doi-asserted-by":"publisher","DOI":"10.2217\/nnm-2018-0110"},{"key":"e_1_2_12_105_1","doi-asserted-by":"publisher","DOI":"10.1002\/btm2.10393"},{"key":"e_1_2_12_106_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msec.2021.112615"},{"issue":"4","key":"e_1_2_12_107_1","article-title":"SRL\u2010Coated PAMAM Dendrimer Nano\u2010Carrier for Targeted Gene Delivery to the Glioma Cells and Competitive Inhibition by Lactoferrin","volume":"15","author":"Najafi F.","year":"2016","journal-title":"Iranian Journal of Pharmaceutical Research"},{"key":"e_1_2_12_108_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2013.05.078"},{"key":"e_1_2_12_109_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2014.12.070"},{"key":"e_1_2_12_110_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2017.08.155"},{"key":"e_1_2_12_111_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5NR02831K"},{"key":"e_1_2_12_112_1","doi-asserted-by":"publisher","DOI":"10.1021\/mp100277h"},{"key":"e_1_2_12_113_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msec.2017.03.309"},{"key":"e_1_2_12_114_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2018.05.027"},{"key":"e_1_2_12_115_1","doi-asserted-by":"publisher","DOI":"10.1177\/0885328220975570"},{"key":"e_1_2_12_116_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2010.09.024"},{"key":"e_1_2_12_117_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2016.09.085"},{"key":"e_1_2_12_118_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2020.117194"},{"key":"e_1_2_12_119_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2016.02.026"},{"key":"e_1_2_12_120_1","doi-asserted-by":"publisher","DOI":"10.1080\/17435889.2026.2665647"},{"key":"e_1_2_12_121_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S531451"},{"key":"e_1_2_12_122_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2026.102951"}],"container-title":["CNS Neuroscience &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cns.71070","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cns.71070","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cns.71070","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:13:16Z","timestamp":1790615596000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cns.71070"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":121,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/cns.71070"],"URL":"https:\/\/doi.org\/10.1002\/cns.71070","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"value":"1755-5930","type":"print"},{"value":"1755-5949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2026-02-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71070"}}