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Therefore, developing approaches to effectively reverse the immunosuppressive TME while enabling accurate HCC imaging poses a major unmet challenge. To tackle this critical challenge, we rationally designed and constructed a hyaluronic acid (HA)-functionalized manganese-doped fluorinated zeolitic imidazolate framework-90 (ZIF-90) nanosystem (ZM-F6@HA NPs) for integrated theranostic applications in HCC. This nanosystem not only enabled noninvasive and precise visualization of HCC lesions through GSH-activatable 1H\/19F MRI for diagnostic purposes, but also induced robust tumor-associated inflammation and promoted potent antitumor adaptive immunity through synergistic mechanisms, including cGAS\u2013STING pathway activation, immunogenic cell death (ICD) induction, and pyroptosis induction in HCC cells. The activated antitumor immune response effectively remodeled the immunosuppressive TME, and its combination with ICIs results in significant tumor regression and substantial inhibition of lung metastasis. This responsive ZIF-90-based multifunctional nanosystem provides a promising and rational strategy for integrated diagnosis and combinatorial immunotherapy of HCC.<\/jats:p>","DOI":"10.1021\/acsami.6c13187","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:01:19Z","timestamp":1790838079000},"page":"54532-54546","source":"Crossref","is-referenced-by-count":0,"title":["Manganese-Doped Fluorinated Zeolitic Imidazolate Framework-90 for Activatable 1H\/19F MRI and Metalloimmunotherapy of Hepatocellular Carcinoma"],"prefix":"10.1021","volume":"18","author":[{"given":"Yuanxi","family":"Zheng","sequence":"first","affiliation":[{"name":"Xiamen University , , ,","place":["Xiamen, China, 361005"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingxuan","family":"Li","sequence":"additional","affiliation":[{"name":"Xiamen University , , ,","place":["Xiamen, China, 361005"]},{"name":"Fujian University of Traditional Chinese Medicine , , ,","place":["Fuzhou, China, 350122"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijia","family":"Fu","sequence":"additional","affiliation":[{"name":"Xiamen University , , ,","place":["Xiamen, China, 361005"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Li","sequence":"additional","affiliation":[{"name":"Xiamen University , , ,","place":["Xiamen, China, 361005"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingxue","family":"Yan","sequence":"additional","affiliation":[{"name":"Xiamen University , , ,","place":["Xiamen, China, 361005"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqin","family":"Chi","sequence":"additional","affiliation":[{"name":"Xiamen University , , ,","place":["Xiamen, China, 361004"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Yin","sequence":"additional","affiliation":[{"name":"Xiamen University , , ,","place":["Xiamen, China, 361004"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5675-8537","authenticated-orcid":true,"given":"Hongyu","family":"Lin","sequence":"additional","affiliation":[{"name":"Xiamen University , , ,","place":["Xiamen, China, 361005"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3215-7013","authenticated-orcid":true,"given":"Jinhao","family":"Gao","sequence":"additional","affiliation":[{"name":"Xiamen University , , ,","place":["Xiamen, China, 361005"]},{"name":"Xiamen University , , ,","place":["Xiamen, China, 361004"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"issue":"10504","key":"2026101404071593300_cit1","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1016\/S0140-6736(25)01042-6","article-title":"The Lancet Commission on addressing the global hepatocellular carcinoma burden: comprehensive strategies from prevention to treatment","volume":"406","author":"Chan","year":"2025","journal-title":"Lancet"},{"issue":"10","key":"2026101404071593300_cit2","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1038\/s41575-019-0186-y","article-title":"A global view of hepatocellular carcinoma: trends, risk, prevention and management","volume":"16","author":"Yang","year":"2019","journal-title":"Nat. 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