{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:58:12Z","timestamp":1791475092108,"version":"4.3.4"},"reference-count":43,"publisher":"Wiley","issue":"56","license":[{"start":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T00:00:00Z","timestamp":1786233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T00:00:00Z","timestamp":1786233600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272802"],"award-info":[{"award-number":["82272802"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82573686"],"award-info":[{"award-number":["82573686"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007452","name":"Wu Jieping Medical Foundation","doi-asserted-by":"publisher","award":["320.6750.2023\u201017\u201019"],"award-info":[{"award-number":["320.6750.2023\u201017\u201019"]}],"id":[{"id":"10.13039\/100007452","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007452","name":"Wu Jieping Medical Foundation","doi-asserted-by":"publisher","award":["320.6750.2025\u201017\u20103"],"award-info":[{"award-number":["320.6750.2025\u201017\u20103"]}],"id":[{"id":"10.13039\/100007452","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007452","name":"Wu Jieping Medical Foundation","doi-asserted-by":"publisher","award":["320.6750.2025\u201026\u201016"],"award-info":[{"award-number":["320.6750.2025\u201026\u201016"]}],"id":[{"id":"10.13039\/100007452","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Materials"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Ammonia death is a recently identified form of regulated cell death with unique molecular mechanisms and prominent anticancer activity. Nevertheless, its efficacy is severely restricted by the absence of tumor\u2010targeted ammonia delivery vehicles and poorly defined immunogenic properties. Herein, we develop a lysosome\u2010targeted ammonia nanogenerator (denoted AlN@HA) to induce ammonia death in hepatocellular carcinoma (HCC) cells and boost HCC immunotherapy. Following CD44 receptor\u2010mediated endocytosis, AlN@HA preferentially accumulates within lysosomes and undergoes in situ hydrolysis to produce excessive ammonia and nanoscopic aluminum hydroxide (Al(OH)\n                    <jats:sub>3<\/jats:sub>\n                    ). Intralysosomal ammonia overload further drives lysosomal alkalinization and membrane permeabilization, autophagic flux blockade, and mitochondrial dysfunction. This sequential signaling cascade elicits tumor cell ammonia death and triggers robust immunogenic cell death. Meanwhile, the hydrolytic byproduct Al(OH)\n                    <jats:sub>3<\/jats:sub>\n                    functions as an intrinsic adjuvant to facilitate dendritic cell maturation. Additionally, ammonia\u2010mediated neutralization of intratumor lactic acid reverses the immunosuppressive tumor microenvironment. In vivo results verify that AlN@HA\u2010initiated ammonia death markedly suppresses local tumor proliferation and activates systemic antitumor immune responses, thereby sensitizing HCC to antiprogrammed cell death 1 immunotherapy. This study clarifies the immunological features of tumor ammonia death, establishes a lysosome\u2010targeted ammonia delivery strategy, and highlights ammonia death as a viable synergistic modality for HCC combination immunotherapy.\n                  <\/jats:p>","DOI":"10.1002\/adma.74542","type":"journal-article","created":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T09:45:38Z","timestamp":1786268738000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lysosome\u2010Targeted Self\u2010Adjuvanting Ammonia Nanogenerator Potentiates Hepatocellular Carcinoma Immunotherapy via Ammonia Death"],"prefix":"10.1002","volume":"38","author":[{"given":"Huichen","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an Shaanxi 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Materials Xi'an Jiaotong University  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mofan","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6831-1417","authenticated-orcid":false,"given":"Xiaobing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Oncology Henan Cancer Hospital &amp; The Affiliated Cancer Hospital of Zhengzhou University  Zhengzhou Henan 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