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Nevertheless, the upregulation of vascular endothelial growth factor A (VEGF\u2010A) and the angiogenesis response triggered by the hypoxic environment following embolization can facilitate tumor recurrence. The combination of TAE\/TACE and anti\u2010angiogenic drugs has become one of the important strategies in the treatment of liver cancer. However, anti\u2010angiogenic strategies using monotherapies that only target VEGF or vascular endothelial growth factor receptor (VEGFR) have limited efficacy in the treatment of HCC. Hence, we designed a degradable embolic microsphere (RegFe@MS) capable of simultaneously loading hydrophobic regorafenib and magnetic iron oxide nanoparticles. Through the \u201ctwo\u2010liquid phase sequential drug loading technology\u201d, RegFe@MS can effectively absorb and encapsulate regorafenib like a sponge. It has been shown that RegFe@MS can inhibit the upregulation of HIF\u20101\u03b1 and the expression of CCR6 through mild hyperthermia, thereby suppressing the release of VEGF\u2010A. In addition, local sustained release of regorafenib can be used to inhibit VEGFR. This strategy can not only inhibit the post\u2010embolization angiogenic response but also maximally suppress the proliferation and invasion of residual tumors. Furthermore, RegFe@MS has demonstrated remarkable therapeutic effects in the rabbit orthotopic liver cancer model.<\/jats:p>","DOI":"10.1002\/adhm.202504261","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T06:58:58Z","timestamp":1766041138000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Degradable Multifunctional Microspheres for Combined Thermotherapy\u2010Embolization\u2010Immune Activation Therapy of Hepatocellular Carcinoma"],"prefix":"10.1002","volume":"15","author":[{"given":"Xuepeng","family":"Lv","sequence":"first","affiliation":[{"name":"State Key Lab of Digital Medical Engineering Jiangsu Laboratory for Biomaterials and Devices School of Biological Science and Medical Engineering Southeast University  Nanjing P. R. 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