Smart responsive Fe/Mn nanovaccine triggers liver cancer immunotherapy via pyroptosis and pyroptosis-boosted cGAS-STING activation

作者全名："Du, Qianying; Luo, Ying; Xu, Lian; Du, Chier; Zhang, Wenli; Xu, Jie; Liu, Yun; Liu, Bo; Chen, Sijin; Wang, Yi; Wang, Zhigang; Ran, Haitao; Wang, Junrui; Guo, Dajing"

作者地址："[Du, Qianying; Luo, Ying; Xu, Lian; Zhang, Wenli; Xu, Jie; Liu, Yun; Liu, Bo; Chen, Sijin; Wang, Yi; Wang, Junrui; Guo, Dajing] Chongqing Med Univ, Dept Radiol, Affiliated Hosp 2, Chongqing 400010, Peoples R China; [Du, Qianying; Luo, Ying; Xu, Lian; Du, Chier; Zhang, Wenli; Wang, Zhigang; Ran, Haitao; Wang, Junrui] Chongqing Med Univ, Chongqing Key Lab Ultrasound Mol Imaging & Dept Ul, Affiliated Hosp 2, Chongqing 400010, Peoples R China"

通信作者："Wang, JR; Guo, DJ (通讯作者)，Chongqing Med Univ, Dept Radiol, Affiliated Hosp 2, Chongqing 400010, Peoples R China.; Wang, JR (通讯作者)，Chongqing Med Univ, Chongqing Key Lab Ultrasound Mol Imaging & Dept Ul, Affiliated Hosp 2, Chongqing 400010, Peoples R China."

来源：JOURNAL OF NANOBIOTECHNOLOGY

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001180669600002

JCR分区：Q1

影响因子：10.6

年份：2024

卷号：22

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Bimetallic nanovaccine; Pyroptosis; cGAS-STING; Hepatocellular carcinoma; Magnetic resonance imaging

摘要："BackgroundThe 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.ResultsA 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.ConclusionThe utilization of metallic nanovaccines to induce pyroptosis-mediated immune activation provides a promising paradigm for HCC treatment."

基金机构："National Natural Science Foundation of China; Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University [CQYC2020030389, 2020-7]; Chongqing Talents Program [cstc2021ycjh-bgzxm0168]; General program of Chongqing Natural Science Foundation [cstc2020jcyj-msxmX1017]; Postdoctoral Innovation Talents Support Program of Chongqing [CQBX202303]; [82271970]; [81971608]"

基金资助正文："This work was supported by the National Natural Science Foundation of China (82271970, 81971608), and the Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University (CQYC2020030389, 2020-7). The authors also appreciate the Chongqing Talents Program (cstc2021ycjh-bgzxm0168), the General program of Chongqing Natural Science Foundation (cstc2020jcyj-msxmX1017) and Postdoctoral Innovation Talents Support Program of Chongqing (CQBX202303). We express our gratitude to BioRender for providing the illustration resources."