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Although TMZ induces cytotoxic DNA methylation in tumor cells, its efficacy is often limited by resistance mechanisms. To overcome these limitations, alternative therapeutic strategies\u2014such as targeting the mitogen\u2010activated protein kinase\/extracellular signal\u2010regulated kinase (MAPK\/ERK) signaling pathway with MEK inhibitors like trametinib and selumetinib\u2014are being explored. However, their clinical success is currently hindered by inadequate delivery across the blood\u2013brain barrier and dose\u2010limiting toxicity. Nanoparticles, particularly positively charged systems, offer enhanced cellular uptake and therapeutic performance due to their strong interactions with negatively charged cell membranes. Cyclodextrin (CyD)\u2010based polymers are promising systems owing to their low toxicity and ability to form inclusion complexes with drugs. In this work, we investigate two cationic CyD polymers as potential nanocarriers for GB therapy based on trametinib and selumetinib. Their multivalent architecture and positive charge can facilitate both the encapsulation of drugs and membrane interactions. These systems present promising candidates for enhancing the efficacy of GB treatment.<\/jats:p>","DOI":"10.1002\/cmdc.202501004","type":"journal-article","created":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T22:38:58Z","timestamp":1771195138000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Positively Charged Polymers Based on Cyclodextrins for Trametinib and Selumetinib Delivery in Glioblastoma Cancer"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3608-1751","authenticated-orcid":false,"given":"Noemi","family":"Bognanni","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze Chimiche Universit\u00e0 degli Studi di Catania  Catania Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4239-5330","authenticated-orcid":false,"given":"Maria Teresa","family":"Gentile","sequence":"additional","affiliation":[{"name":"Department of Environmental Biological and Pharmaceutical Sciences and Technologies University of Campania \u201cLuigi Vanvitelli\u201d  Caserta Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0436-4621","authenticated-orcid":false,"given":"Antonia","family":"Feola","sequence":"additional","affiliation":[{"name":"Dipartimento di Biologia Universit\u00e0 degli Studi di Napoli \u201cFederico II\u201d  Napoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Giglio","sequence":"additional","affiliation":[{"name":"Institute for Polymers, Composites and Biomaterials CNR\u2010IPCB  Catania Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Dragone","sequence":"additional","affiliation":[{"name":"Department of Environmental Biological and Pharmaceutical Sciences and Technologies University of Campania \u201cLuigi Vanvitelli\u201d  Caserta Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1504-2479","authenticated-orcid":false,"given":"Carla","family":"Isernia","sequence":"additional","affiliation":[{"name":"Department of Environmental Biological and Pharmaceutical Sciences and Technologies University of Campania \u201cLuigi Vanvitelli\u201d  Caserta Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8305-081X","authenticated-orcid":false,"given":"Graziella","family":"Vecchio","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Chimiche Universit\u00e0 degli Studi di Catania  Catania Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,15]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2024.101122"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-025-02046-4"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmt.2023.09.001"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.3c00705"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msec.2016.09.016"},{"key":"e_1_2_10_7_1","doi-asserted-by":"crossref","unstructured":"K. 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