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Cell Membrane Hybrid Lipid Nanovesicles Enhance Innate Immunity for Synergistic Immunotherapy by Promoting Immunogenic Cell Death and cGAS Activation

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机构: [1]Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. [2]Department of Immuno-Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China. [3]Department of Nuclear Medicine, The First Affiliated Hospital, College of Medicine, Henan Medical Key Laboratory of Molecular Imaging, Zhengzhou University, Jianshe East Road, Zhengzhou 450052, Henan, China. [4]Department of Medical Technology, Nanyang Medical College, 1106 Xuefeng West Road, Nanyang 473000, Henan, China. [5]Department of Nuclear Medicine, Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China. [6]Department of Nuclear Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China. [7]Department of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China. [8]Department of Breast and Thyroid Surgery, The Second People's Hospital of Lianyungang, Lianyungang, China. [9]Department of Radiology, Beijing Jingmei Group General Hospital, Beijing, China.
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Immunotherapy shows great therapeutic potential for long-term protection against tumor relapse and metastasis. Innate immune sensors, such as cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING), dissolve DNA and induce type I interferon. Through activation of the cGAS/STING pathway, chemotherapy drugs and reversine (REV) may provide synergetic anti-tumor effects. Here, we prepared drug-loaded cell membrane hybrid lipid nanovesicles (LEVs) (designated LEV@DOX@REV) by fusion of cell membranes, phospholipids, doxorubicin (DOX), and REV, to realize accurate delivery to tumors and chemo-immunotherapy. The cell membranes of LEVs confer "homing" abilities. DOX can induce immunogenic cell death as a result of its specific immunomodulatory effects, which promotes the maturation of immune cells and improves the microenvironment of the immune system. REV is proven to efficiently activate cGAS/STING signaling, thereby enhancing the immune system. The antitumor efficacy of LEV@DOX@REV was evaluated in a 4T1 subcutaneous tumor xenograft model, a distant metastatic tumor model, and a liver metastatic tumor model. LEV@DOX@REV facilitated the infiltration of cytotoxic T lymphocytes within tumors, increased the secretion of proinflammatory cytokines, and modified the tumor microenvironment. In conclusion, LEV@DOX@REV displayed favorable antitumor effects and extended the survival of tumor-bearing mice. We therefore successfully developed nanoparticles capable of enhancing immune activation that have potential therapeutic applications for cancer immunotherapy.Copyright © 2024 Ruijie Qian et al.

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出版当年[2025]版:
大类 | 2 区 医学
小类 | 2 区 工程:生物医学 2 区 材料科学:生物材料
最新[2025]版:
大类 | 2 区 医学
小类 | 2 区 工程:生物医学 2 区 材料科学:生物材料
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出版当年[2024]版:
Q1 ENGINEERING, BIOMEDICAL Q1 MATERIALS SCIENCE, BIOMATERIALS
最新[2024]版:
Q1 ENGINEERING, BIOMEDICAL Q1 MATERIALS SCIENCE, BIOMATERIALS

影响因子: 最新[2024版] 最新五年平均 出版当年[2024版] 出版当年五年平均 出版前一年[2023版]

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第一作者机构: [1]Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
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