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In a retrospective analysis, we found a notable downregulation of glutathione peroxidase 2 (GPX2) in KRAS G13D\u2010 mutant colorectal cancer (CRC), which correlated with poor outcomes. We hypothesized that GPX2 acts as a tumor suppressor and that its restoration could render KRAS G13D\u2010driven tumors vulnerable. In this study, we developed a selenium nanoparticle (SeNPs)\u2010based nanostrategy to suppress KRAS G13D\u2010driven tumors by modulating GPX2 expression. SeNPs upregulated GPX2 expression, thereby inhibiting metastasis through the GPX2\u2010HIF1\u03b1\u2010VEGF axis. Moreover, SeNPs release selenite (SeO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>2\u2212<\/jats:sup>\n                    ) in situ, which interacts with the mutant pocket (residues 13\u201317) of the KRAS G13D protein. In vivo, this multimodal strategy demonstrated exceptional efficacy. In orthotopic CRC models, SeNPs significantly inhibited primary tumor growth and effectively prevented liver metastasis. In cell\u2011derived xenograft (CDX) and patient\u2010derived xenograft (PDX) models, SeNPs achieved tumor inhibition rates of 70% and 61%, respectively. Collectively, this study demonstrates the first\u2010in\u2010class therapeutic potential of SeNPs against this recalcitrant KRAS mutant and provides a novel nanoplatform for KRAS G13D\u2010targeted therapy.\n                  <\/jats:p>","DOI":"10.1002\/advs.202523795","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T11:11:06Z","timestamp":1787051466000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Selenium Nanoparticles Selectively Target KRAS G13D to Inhibit Colorectal Cancer"],"prefix":"10.1002","author":[{"given":"Xiaoting","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Surgery School of Medicine Xiang'an Hospital of Xiamen University Xiamen University  Xiamen Fujian China"},{"name":"Department of Gastrointestinal Surgery The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou Guangdong 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