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However, the lack of targeted intervention for intracellular copper may induce systemic side effects, hindering the application of cuproptosis in tumor therapy. Herein, we constructed a targeted copper ion delivery system (Cu\u2010Lip\u2010Gal(H)) based on galactose\u2010modified thermosensitive liposomes, combined with local tumor hyperthermia targeted copper delivery into hepatocellular carcinoma (HCC) cells. Cu\u2010Lip\u2010Gal showed excellent physicochemical properties and 42\u00b0C thermosensitive release, with 64.67% \u00b1 2.52% cumulative release within 0.5 h. The Cu\u2010Lip\u2010Gal(H) group reduced HepG2 and Huh7 cell viability to 24.48% \u00b1 3.31% and 18.00% \u00b1 3.18%, respectively; it exhibited 5.8\u2010fold higher intracellular copper concentration in HepG2 cells and 5.2\u2010fold higher in Huh7 cells. In nude mouse xenografts, Cu\u2010Lip\u2010Gal(H) achieved a tumor inhibition rate of 86.7% \u00b1 1.9% without obvious histopathological changes in major organs but significantly increased necrotic cells in tumors along with the highest FDX1 expression levels observed in this study. These findings provide new insights into cuproptosis\u2010based copper ion delivery systems for HCC treatment.<\/jats:p>","DOI":"10.1002\/mco2.71068","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:35:58Z","timestamp":1791876958000},"source":"Crossref","is-referenced-by-count":0,"title":["Hepatocellular Carcinoma Targeted Thermosensitive Cu\n                    <sup>2+<\/sup>\n                    Liposomes Based on the Cuproptosis Mechanism"],"prefix":"10.1002","volume":"7","author":[{"given":"Hao","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology Peking University Cancer Hospital (Inner Mongolia Campus) &amp; Affiliated Cancer Hospital of Inner Mongolia Medical University Inner Mongolia Autonomous Region  Hohhot China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Pediatric Maternal and Child Health 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