biostudies-literatureDu Qthe Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical Universitythe General program of Chongqing Natural Science FoundationNational Natural Science Foundation of Chinathe Chongqing Talents Program95https://www.ebi.ac.uk/biostudies/studies/S-EPMC10918897biostudies-literatureUnknown22(1)<h4>Background</h4>The prognosis for hepatocellular carcinoma (HCC) remains suboptimal, characterized by high recurrence and metastasis rates. Although metalloimmunotherapy has shown potential in combating tumor proliferation, recurrence and metastasis, current apoptosis-based metalloimmunotherapy fails to elicit sufficient immune response for HCC.<h4>Results</h4>A smart responsive bimetallic nanovaccine was constructed to induce immunogenic cell death (ICD) through pyroptosis and enhance the efficacy of the cGAS-STING pathway. The nanovaccine was composed of manganese-doped mesoporous silica as a carrier, loaded with sorafenib (SOR) and modified with MIL-100 (Fe), where Fe³⁺, SOR, and Mn²⁺ were synchronized and released into the tumor with the help of the tumor microenvironment (TME). Afterward, Fe³⁺ worked synergistically with SOR-induced immunogenic pyroptosis (via both the classical and nonclassical signaling pathways), causing the outflow of abundant immunogenic factors, which contributes to dendritic cell (DC) maturation, and the exposure of double-stranded DNA (dsDNA). Subsequently, the exposed dsDNA and Mn²⁺ jointly activated the cGAS-STING pathway and induced the release of type I interferons, which further led to DC maturation. Moreover, Mn²⁺-related T1 magnetic resonance imaging (MRI) was used to visually evaluate the smart response functionality of the nanovaccine.<h4>Conclusion</h4>The utilization of metallic nanovaccines to induce pyroptosis-mediated immune activation provides a promising paradigm for HCC treatment.Journal of nanobiotechnologySmart responsive Fe/Mn nanovaccine triggers liver cancer immunotherapy via pyroptosis and pyroptosis-boosted cGAS-STING activation.PMC1091889781971608cstc2020jcyj-msxmX101782271970CQYC2020030389, 2020-7cstc2021ycjh-bgzxm0168Xu LDu QWang JXu JZhang WLiu YDu CRan HLuo YLiu BGuo DChen SWang YWang ZfalseSmart responsive Fe/Mn nanovaccine triggers liver cancer immunotherapy via pyroptosis and pyroptosis-boosted cGAS-STING activation.<h4>Background</h4>The prognosis for hepatocellular carcinoma (HCC) remains suboptimal, characterized by high recurrence and metastasis rates. Although metalloimmunotherapy has shown potential in combating tumor proliferation, recurrence and metastasis, current apoptosis-based metalloimmunotherapy fails to elicit sufficient immune response for HCC.<h4>Results</h4>A smart responsive bimetallic nanovaccine was constructed to induce immunogenic cell death (ICD) through pyroptosis and enhance the efficacy of the cGAS-STING pathway. The nanovaccine was composed of manganese-doped mesoporous silica as a carrier, loaded with sorafenib (SOR) and modified with MIL-100 (Fe), where Fe³⁺, SOR, and Mn²⁺ were synchronized and released into the tumor with the help of the tumor microenvironment (TME). Afterward, Fe³⁺ worked synergistically with SOR-induced immunogenic pyroptosis (via both the classical and nonclassical signaling pathways), causing the outflow of abundant immunogenic factors, which contributes to dendritic cell (DC) maturation, and the exposure of double-stranded DNA (dsDNA). Subsequently, the exposed dsDNA and Mn²⁺ jointly activated the cGAS-STING pathway and induced the release of type I interferons, which further led to DC maturation. Moreover, Mn²⁺-related T1 magnetic resonance imaging (MRI) was used to visually evaluate the smart response functionality of the nanovaccine.<h4>Conclusion</h4>The utilization of metallic nanovaccines to induce pyroptosis-mediated immune activation provides a promising paradigm for HCC treatment.2024-01-01T00:00:00Z2024 Mar2026-06-12T10:09:55.381Z2025-04-04T12:35:35.711ZS-EPMC109188973844895910.1186/s12951-024-02354-2