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The combination of immunostimulatory chemotherapeutics represents a promising strategy to enhance the effectiveness of immunotherapy. However, it is hampered by the poor delivery of conventional chemotherapeutics. Here, it is shown that H\u2010ferritin nanocages loaded with doxorubicin (DOX@HFn) show potent chemo\u2010immunotherapy in hepatocellular carcinoma tumor models. DOX@HFn is constructed with uniform size, high stability, favorable drug loading, and intracellular acidity\u2010driven drug release. The receptor\u2010mediated targeting of DOX@HFn to liver cancer cells promote cellular uptake and tumor penetration in vitro and in vivo. DOX@HFn triggers immunogenic cell death to tumor cells and promotes the subsequent activation and maturation of dendritic cells. In vivo studies in H22 subcutaneous hepatoma demonstrate that DOX@HFn significantly inhibits the tumor growth with &gt;30% tumors completely eliminated, while alleviating the systemic toxicity of free DOX. DOX@HFn also exhibits robust antitumor immune response and tumoricidal effect in a more aggressive Hepa1\u20106 orthotopic liver tumor model, which is confirmed by the in situ magnetic resonance imaging and transcriptome sequencing. This study provides a facile and robust strategy to improve therapeutic efficacy of liver cancer.<\/jats:p>","DOI":"10.1002\/smtd.202201086","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T01:06:10Z","timestamp":1669770370000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Ferritin Nanocaged Doxorubicin Potentiates Chemo\u2010Immunotherapy against Hepatocellular Carcinoma via Immunogenic Cell Death"],"prefix":"10.1002","volume":"7","author":[{"given":"Yang","family":"Chen","sequence":"first","affiliation":[{"name":"School of Medicine South China University of Technology  Guangzhou Guangdong 510006 China"},{"name":"Department of Clinical Laboratory The First Affiliated Hospital of Nanchang University  Nanchang Jiangxi 330006 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