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However, its application in glioblastoma (GBM) is hindered by the diminished capacity of CDT agents to traverse the blood\u2013brain barrier (BBB), inadequate tumour targeting efficiency, and restricted availability of H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> within the tumour microenvironment (TME). To address these challenges, we devised a novel CDT agent (Fe@tFNAs\u2010ANG\u20103AT) based on a tetrahedral framework nucleic acids (tFNAs). Fe@tFNAs\u2010ANG\u20103AT was constructed by anchoring iron ions (Fe<jats:sup>3+<\/jats:sup>) onto the dual appendages\u2010modified tFNAs. Specifically, one appendage, Angiopep\u20102 (ANG, a penetrating peptide), facilitates Fe@tFNAs\u2010ANG\u20103AT penetration across the BBB and selective targeting of tumour cells. Simultaneously, the second appendage, 3\u2010Amino\u20101,2,4\u2010triazole (3AT, a H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> enzyme inhibitor), augments the H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> levels required for effective CDT treatment. Upon tumour cell internalization, the loaded Fe<jats:sup>3+<\/jats:sup> in Fe@tFNAs\u2010ANG\u20103AT is reduced to Fe<jats:sup>2+<\/jats:sup> by the overexpressed glutathione (GSH) in the TME, catalysing the generation of cytotoxic hydroxyl radicals (\u00b7OH) and inducing tumour cell death via elevated oxidative stress levels within tumour cells. It is anticipated that Fe@tFNAs\u2010ANG\u20103AT holds promise as a transformative treatment strategy for GBM.<\/jats:p>","DOI":"10.1111\/cpr.13736","type":"journal-article","created":{"date-parts":[[2024,8,24]],"date-time":"2024-08-24T13:39:28Z","timestamp":1724506768000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["A novel tetrahedral framework nucleic acid\u2010derived chemodynamic therapy agent for effective glioblastoma treatment"],"prefix":"10.1111","volume":"58","author":[{"given":"Xiaodie","family":"Li","sequence":"first","affiliation":[{"name":"Department of Oncology, Zhujiang Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Zhujiang Hospital Southern Medical University  Guangzhou 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