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Cholesterol\u2010rich tumor fragments significantly contribute to IRTM deterioration. This study developed a cholesterol\u2010targeted catalytic hydrogel, DA\u2010COD\u2010OD\u2010HCS, to enhance the synergy between MWA and immune checkpoint inhibitors (ICIs) for HCC treatment. Cholesterol oxidase (COD), modified with dimethyl maleic anhydride (DA) for release in acidic IRTM, is used to degrade cholesterol. Oxydextran (OD) and hemin\u2010chitosan (HCS) formed a dual network gel, ensuring long\u2010term fixation of COD and hemin in the IRTM post\u2010MWA. In both in vitro and in vivo HCC models, DA\u2010COD\u2010OD\u2010HCS effectively released COD, degraded cholesterol, and induced tumor cell ferroptosis, enhancing the antitumor immune response. Combined with anti\u2010PD\u2010L1 immunotherapy, this strategy inhibited primary tumor growth and distant metastases, without side effects on adjacent tissues. This work highlights that cholesterol\u2010targeting catalytic hydrogels fueled by tumor debris can significantly improve the efficacy of MWA and ICIs, offering a novel therapeutic approach for HCC.<\/jats:p>","DOI":"10.1002\/advs.202406975","type":"journal-article","created":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T04:34:02Z","timestamp":1733978042000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Cholesterol Targeted Catalytic Hydrogel Fueled by Tumor Debris can Enhance Microwave Ablation Therapy and Anti\u2010Tumor Immune Response"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0752-8292","authenticated-orcid":false,"given":"Lin","family":"Shen","sequence":"first","affiliation":[{"name":"Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology The Fifth Affiliated Hospital of Wenzhou Medical University  Lishui 323000 P. 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