{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T00:52:39Z","timestamp":1793321559828,"version":"4.5.0"},"reference-count":46,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012151","name":"Sanming Project of Medicine in Shenzhen","doi-asserted-by":"publisher","award":["SZSM202211011"],"award-info":[{"award-number":["SZSM202211011"]}],"id":[{"id":"10.13039\/501100012151","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["iMeta"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Hepatocellular carcinoma (HCC) is associated with high mortality rates despite the widespread application of radiofrequency ablation (RFA), which has limited therapeutic efficacy as a monotherapy. This study investigated ribonucleotide reductase M2 (\n                    <jats:italic>RRM2<\/jats:italic>\n                    ) upregulation in post\u2010RFA HCC tissues and developed a targeted nanoco\u2010delivery system (red blood cell membrane\/cRGD\u2010modified pH\u2010sensitive liposomes [sS@RBCM\/cRGD\u2010phLips]) to increase RFA efficacy through specific\n                    <jats:italic>RRM2<\/jats:italic>\n                    knockout.\n                    <jats:italic>RRM2<\/jats:italic>\n                    knockout synergistically amplified RFA\u2010induced tumor cell death by promoting ferroptosis and immunogenic cell death. Mechanistically,\n                    <jats:italic>RRM2<\/jats:italic>\n                    knockout upregulated the STAT1\u2013IRF1\u2013ACSL4 axis, which potentiated lipid peroxidation and ferroptosis. Furthermore, the nanocarrier system enhanced dendritic cell maturation and cytotoxic T cell infiltration, thereby remodeling the tumor immune microenvironment. In vivo experiments revealed that the combination of RFA and RRM2\u2010targeted nanoparticles significantly suppressed tumor growth and prolonged survival in HCC\u2010bearing mice with minimal systemic toxicity. Notably, the dual\u2010loaded nanoparticles also enhanced the efficacy of anti\u2010programmed cell death protein 1 therapy, suggesting a promising combinatorial approach for HCC treatment. This study presents a novel therapeutic strategy that integrates\n                    <jats:italic>RRM2<\/jats:italic>\n                    \u2010targeted gene editing with RFA, offering a robust and synergistic approach for improving HCC outcomes.\n                  <\/jats:p>","DOI":"10.1002\/imt2.70067","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T01:03:42Z","timestamp":1754528622000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["RRM2\u2010targeted nanocarrier enhances radiofrequency ablation efficacy in hepatocellular carcinoma through ferroptosis amplification and immune remodeling"],"prefix":"10.1002","volume":"4","author":[{"given":"Weiliang","family":"Hou","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Shanghai Institute of Pancreatic Diseases, National Key Laboratory of Immunity and Inflammation, Changhai Clinical Research Unit, 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