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While it exhibits potent anticancer activity, its clinical application is hindered by systemic toxicity and limited tissue specificity. In this study, an advanced therapeutic approach is developed using arsenic prodrug\u2010loaded bimetallic sulfide MnZnS\n                    <jats:sub>X<\/jats:sub>\n                    nanorods (As\u2010MnZnS\n                    <jats:sub>X<\/jats:sub>\n                    NRs) to enhance both the efficacy and safety of As\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>3<\/jats:sub>\n                    in hepatocellular carcinoma treatment. These nanorods are engineered to release Mn\n                    <jats:sup>2+<\/jats:sup>\n                    and H\n                    <jats:sub>2<\/jats:sub>\n                    S within the tumor microenvironment, facilitating binary\u2010cooperative activation of the cGAS\u2010STING pathway. This dual activation mechanism enhances immune responses while converting the arsenic prodrug into its cytotoxic form, As\n                    <jats:sup>III<\/jats:sup>\n                    . The results demonstrate that Mn\n                    <jats:sup>2+<\/jats:sup>\n                    amplifies the cGAS\u2010STING pathway by inducing TBK1 phosphorylation and IRF3 activation, leading to dendritic cell maturation and improved tumor antigen cross\u2010presentation. Simultaneously, H\n                    <jats:sub>2<\/jats:sub>\n                    S promotes prodrug conversion and enhances immune activation, collectively driving binary stimulation of the cGAS\u2010STING pathway. This strategy significantly augments the antitumor efficacy of As\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>3<\/jats:sub>\n                    by integrating immune modulation with targeted cytotoxic effects. Furthermore, MnZnS\n                    <jats:sub>X<\/jats:sub>\n                    nanorods enable in vivo MRI, allowing real\u2010time monitoring of treatment progression. This study represents a substantial advancement in liver cancer therapy by integrating chemoimmunotherapy with diagnostic imaging, thereby improving therapeutic precision while minimizing systemic toxicity.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202404238","type":"journal-article","created":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T04:11:37Z","timestamp":1740543097000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Bimetallic MnZnS\n                    <sub>X<\/sub>\n                    Nanotheranostics for Self\u2010Activatable Chemo\u2010Immunotherapy of Hepatocellular Carcinoma via H\u2082S\u2010Triggered Arsenic Prodrug Activation and Binary cGAS\u2010STING Pathway Modulation"],"prefix":"10.1002","volume":"14","author":[{"given":"WeiYi","family":"Cheng","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences Zhejiang Chinese Medical University  Hangzhou 310053 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuqi","family":"Peng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Infectious Disease Vaccine Development Xiang'an Biomedicine Laboratory National Innovation Platform for Industry\u2010Education Integration in Vaccine Research Center for Molecular Imaging and Translational Medicine School of Public Health Xiamen University  Xiamen 361102 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"He","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Zhejiang Chinese Medical University  Hangzhou 310053 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"WeiYe","family":"Ren","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Zhejiang Chinese Medical University  Hangzhou 310053 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JingQuan","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Zhejiang Chinese Medical University  Hangzhou 310053 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"XiaoQian","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Zhejiang Chinese Medical University  Hangzhou 310053 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Dermatology &amp; 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