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Here, we developed tellurium\u2010selenium nanoparticles (TeSe NPs) with exceptional near\u2010infrared (NIR) chiroptical properties and potent antitumor activity against drug\u2010resistant glioma for the first time. Notably, the right\u2010handed nanoparticles (\n                    <jats:italic>D<\/jats:italic>\n                    \u2010TeSe NPs) exhibited higher cellular uptake than left\u2010handed\n                    <jats:italic>L<\/jats:italic>\n                    \u2010TeSe NPs through chirality\u2010selective recognition by drug\u2010resistant glioma cells. The Te and Se active centers in\n                    <jats:italic>D<\/jats:italic>\n                    \u2010TeSe NPs selectively triggered severe oxidative stress in glioma cells, leading to redox imbalance, reactive oxygen species (ROS)\u2010mediated mitochondrial dysfunction, and ultimately causing 44.2% glioma cell death (versus 37.1% for\n                    <jats:italic>L<\/jats:italic>\n                    \u2010TeSe NPs). When combined with 808\u00a0nm right\u2010handed circularly polarized light,\n                    <jats:italic>D<\/jats:italic>\n                    \u2010TeSe NPs showed enhanced ROS generation, elevating therapeutic efficacy to 62.5% while maintaining negligible toxicity to normal cells. Furthermore, apolipoprotein E\u2010functionalized\n                    <jats:italic>D<\/jats:italic>\n                    \u2010TeSe NPs demonstrated improved BBB penetration and tumor\u2010targeting capability, significantly extending the survival of mice with orthotopic drug\u2010resistant glioma to 52 days (versus 21 days for PBS control). This study pioneers a NIR and brain\u2010targeted chiral nanoplatform for precision therapy of orthotopic glioma, offering a chirality\u2010driven paradigm against drug\u2010resistant malignancies and other brain diseases.\n                  <\/jats:p>","DOI":"10.1002\/anie.202516990","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T11:57:16Z","timestamp":1760097436000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Brain\u2010Targeted Near\u2010Infrared Chiral TeSe Nanodrug Against Orthotopic Drug\u2010Resistant Glioma"],"prefix":"10.1002","volume":"65","author":[{"given":"Yisheng","family":"Liu","sequence":"first","affiliation":[{"name":"Key Laboratory for Special Functional Materials of Ministry of Education Henan University  Kaifeng Henan 475004 China"},{"name":"Department of Clinical Laboratory of Huaihe Hospital, School of Life Sciences Henan University  Kaifeng Henan 475004 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory of Huaihe Hospital, School of Life Sciences Henan University  Kaifeng Henan 475004 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingxiang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory of Huaihe Hospital, School of Life Sciences Henan University  Kaifeng Henan 475004 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Zhong","sequence":"additional","affiliation":[{"name":"Key Laboratory for Special Functional Materials of Ministry of Education Henan University  Kaifeng Henan 475004 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuhong","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory of Huaihe Hospital, School of Life Sciences Henan University  Kaifeng Henan 475004 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoqun","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory of Huaihe Hospital, School of Life Sciences Henan University  Kaifeng Henan 475004 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cai","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory of Huaihe Hospital, School of Life Sciences Henan University  Kaifeng Henan 475004 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jincheng","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory of Huaihe Hospital, School of Life Sciences Henan University  Kaifeng Henan 475004 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinqin","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory of Huaihe 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