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Its clinical application, however, is limited by challenges, such as precise dosage control and eliciting effective immune responses. To overcome these hurdles, a dual\u2010response strategy is devised that integrates H\n                    <jats:sub>2<\/jats:sub>\n                    S therapy with intracellular magnetic hyperthermia (IMH) to synergistically enhance anti\u2010tumor immunity. This approach is centered on the development of Zn\n                    <jats:sub>0.4<\/jats:sub>\n                    Fe\n                    <jats:sub>2.6<\/jats:sub>\n                    O\n                    <jats:sub>4<\/jats:sub>\n                    @L\u2010Cys, a high\u2010performance nanotherm agent that responds to both the acidic lysosomal environment and an exogenous alternating magnetic field. At the tumor site, Zn\n                    <jats:sub>0.4<\/jats:sub>\n                    Fe\n                    <jats:sub>2.6<\/jats:sub>\n                    O\n                    <jats:sub>4<\/jats:sub>\n                    @L\u2010Cys nanoparticles release the H\n                    <jats:sub>2<\/jats:sub>\n                    S donor L\u2010cysteine (L\u2010Cys) in a controlled manner, facilitating localized H\n                    <jats:sub>2<\/jats:sub>\n                    S generation. This dual\u2010response strategy enhances anti\u2010tumor immunity through two key mechanisms: 1) inhibiting catalase expression and accelerating hydroxyl radical production, thereby amplifying IMH\u2010induced immunological effects; and 2) alleviating tumor immunosuppression by reducing myeloid\u2010derived suppressor cell accumulation, promoting immune cell infiltration, and selectively inducing tumor cell apoptosis. Experimental findings demonstrate that this strategy not only strengthens anti\u2010tumor immunity but also improves therapeutic efficacy while minimizing off\u2010target effects. Beyond confirming the synergy between H\n                    <jats:sub>2<\/jats:sub>\n                    S therapy and IMH in hepatocellular carcinoma treatment, these results provide valuable insights for developing integrated tumor treatment approaches.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202501617","type":"journal-article","created":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T03:10:04Z","timestamp":1750648204000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Intracellular Magnetic Nanodelivery of H\n                    <sub>2<\/sub>\n                    S and Heat Synergize to Reshape the Tumor Immune Microenvironment"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4389-0595","authenticated-orcid":false,"given":"Lijun","family":"Dai","sequence":"first","affiliation":[{"name":"Key Laboratory of Western Resources Biology and Modern Biotechnology Ministry of Education School of Life Sciences and Medicine Northwest University  Xi'an Shaanxi 710069 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wangbo","family":"Jiao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education College of Chemistry and Materials Science Northwest University  Xi'an 710127 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education College of Chemistry and Materials Science Northwest University  Xi'an 710127 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongqiang","family":"He","sequence":"additional","affiliation":[{"name":"Key Laboratory of Western Resources Biology and Modern Biotechnology Ministry of Education School of Life Sciences and Medicine Northwest University  Xi'an Shaanxi 710069 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoyi","family":"Lu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Western Resources Biology and Modern Biotechnology Ministry of Education School of Life Sciences and Medicine Northwest University  Xi'an Shaanxi 710069 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengxiang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Western Resources Biology and Modern Biotechnology Ministry of Education School of Life Sciences and Medicine Northwest University  Xi'an Shaanxi 710069 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugang","family":"Li","sequence":"additional","affiliation":[{"name":"Shaanxi Provincial Key Laboratory of Magnetic Medicine Shaanxi Province Center for Regenerative Medicine and Surgery Engineering Research National Local Joint Engineering Research Center for Precision Surgery &amp; Regenerative Medicine Institute of Regenerative and Reconstructive Medicine Med\u2010X Research Institute First Affiliated Hospital of Xi'an Jiaotong University  Xi'an 710061 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyao","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Western Resources Biology and Modern Biotechnology Ministry of Education School of Life Sciences and Medicine Northwest University  Xi'an Shaanxi 710069 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Yan","sequence":"additional","affiliation":[{"name":"Shaanxi Provincial Key Laboratory of Magnetic Medicine Shaanxi Province Center for Regenerative Medicine and Surgery Engineering Research National Local Joint Engineering Research Center for Precision Surgery &amp; Regenerative Medicine Institute of Regenerative and Reconstructive Medicine Med\u2010X Research Institute First Affiliated Hospital of Xi'an Jiaotong University  Xi'an 710061 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Lv","sequence":"additional","affiliation":[{"name":"Shaanxi Provincial Key Laboratory of Magnetic Medicine Shaanxi Province Center for Regenerative Medicine and Surgery Engineering Research National Local Joint Engineering Research Center for Precision Surgery &amp; 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