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Nanotechnology offers unique opportunities to develop innovative and more effective therapeutic approaches. However, most nanosystems developed to treat glioblastomas, especially those based on metallic nanoparticles (NPs), have proven unsuccessful due to their inability to efficiently target these tumors, which are particularly inaccessible due to the restrictions imposed by the blood\u2010brain tumor barrier (BBTB). Here, an innovative strategy is presented to efficiently target metallic NPs to glioblastomas through glucose transporters (GLUT) overexpressed on the endothelial cells of glioblastoma microvasculature, particularly GLUT1. Specifically, Iron Oxide Nanoparticles (IONPs) are functionalized with glucuronic acid to promote GLUT\u2010mediated transcytosis which is drastically boosted by inducing mild hypoglycemia. This metabolically\u2010driven active targeting strategy has yielded unprecedented efficacy in targeting metallic NPs to glioblastomas. Moreover, these IONPs, designed to act as magnetic hyperthermia (MH) mediators, are used to conduct a proof\u2010of\u2010concept preclinical study on MRI\u2010tracked MH therapy following intravenous administration, resulting in significant tumor growth delay. These findings demonstrate unparalleled efficiency in glioblastoma targeting and lay the ground for developing alternative therapeutic strategies to combat glioblastoma.<\/jats:p>","DOI":"10.1002\/adhm.202404391","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T23:15:29Z","timestamp":1732317329000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Metabolically\u2010Driven Active Targeting of Magnetic Nanoparticles Functionalized with Glucuronic Acid to Glioblastoma: Application to MRI\u2010Tracked Magnetic Hyperthermia Therapy"],"prefix":"10.1002","volume":"14","author":[{"given":"Carlos","family":"Caro","sequence":"first","affiliation":[{"name":"Biomedical Magnetic Resonance Laboratory\u2010BMRL Andalusian Public Foundation Progress and Health\u2010FPS Seville 41092 Spain"},{"name":"Biomedical Research Institute of Malaga and Nanomedicine Platform (IBIMA\u2010BIONAND Platform) University of Malaga  C\/Severo Ochoa, 35 Malaga 29590 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 M.","family":"Paez\u2010Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Biomedical Magnetic Resonance Laboratory\u2010BMRL Andalusian Public Foundation Progress and Health\u2010FPS Seville 41092 Spain"},{"name":"Biomedical Research Institute of Malaga and Nanomedicine Platform (IBIMA\u2010BIONAND Platform) University of Malaga  C\/Severo Ochoa, 35 Malaga 29590 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Pern\u00eda Leal","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica y Farmac\u00e9utica Facultad de Farmacia Universidad de Sevilla  C\/ Profesor Garc\u00eda Gonz\u00e1lez 2 Seville 41012 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Carayol","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute of Malaga and Nanomedicine Platform (IBIMA\u2010BIONAND Platform) University of Malaga  C\/Severo Ochoa, 35 Malaga 29590 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica","family":"Feijoo\u2010Cuaresma","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute of Malaga and Nanomedicine Platform (IBIMA\u2010BIONAND Platform) University of Malaga  C\/Severo Ochoa, 35 Malaga 29590 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2257-7682","authenticated-orcid":false,"given":"Mar\u00eda L.","family":"Garc\u00eda\u2010Mart\u00edn","sequence":"additional","affiliation":[{"name":"Biomedical Magnetic Resonance Laboratory\u2010BMRL Andalusian Public Foundation Progress and Health\u2010FPS Seville 41092 Spain"},{"name":"Biomedical Research Institute of Malaga and Nanomedicine Platform (IBIMA\u2010BIONAND Platform) University of Malaga  C\/Severo Ochoa, 35 Malaga 29590 Spain"},{"name":"Biomedical Research Networking Center in Bioengineering Biomaterials &amp; 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