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Topics {✒️}

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Schema {🗺️}

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         headline:Inhibition of post-surgery tumour recurrence via a sprayable chemo-immunotherapy gel releasing PD-L1 antibody and platelet-derived small EVs
         description:Melanoma is the most serious type of skin cancer, and surgery is an effective method to treat melanoma. Unfortunately, local residual micro-infiltrated tumour cells and systemic circulating tumour cells (CTCs) are significant causes of treatment failure, leading to tumour recurrence and metastasis. Small EVs were isolated from platelets by differential centrifugation, and doxorubicin-loaded small EVs (PexD) was prepared by mixing small EVs with doxorubicin (DOX). PexD and an anti-PD-L1 monoclonal antibody (aPD-L1) were co-encapsulated in fibrin gel. The synergistic antitumour efficacy of the gel containing PexD and aPD-L1 was assessed both in vitro and in vivo. Herein, we developed an in situ-formed bioresponsive gel combined with chemoimmunotherapeutic agents as a drug reservoir that could effectively inhibit both local tumour recurrence and tumour metastasis. In comparison with a DOX solution, PexD could better bind to tumour cells, induce more tumour immunogenic cell death (ICD) and promote a stronger antitumour immune response. PexD could enter the blood circulation through damaged blood vessels to track and eliminate CTCs. The concurrent release of aPD-L1 at the tumour site could impair the PD-1/PD-L1 pathway and restore the tumour-killing effect of cytotoxic T cells. This chemoimmunotherapeutic strategy triggered relatively strong T cell immune responses, significantly improving the tumour immune microenvironment. Our findings indicated that the immunotherapeutic fibrin gel could “awaken” the host innate immune system to inhibit both local tumour recurrence post-surgery and metastatic potential, thus, it could serve as a promising approach to prevent tumour recurrence.
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            Metastasis
            Drug reservoir
            Platelet-derived small EVs
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            Biotechnology
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      headline:Inhibition of post-surgery tumour recurrence via a sprayable chemo-immunotherapy gel releasing PD-L1 antibody and platelet-derived small EVs
      description:Melanoma is the most serious type of skin cancer, and surgery is an effective method to treat melanoma. Unfortunately, local residual micro-infiltrated tumour cells and systemic circulating tumour cells (CTCs) are significant causes of treatment failure, leading to tumour recurrence and metastasis. Small EVs were isolated from platelets by differential centrifugation, and doxorubicin-loaded small EVs (PexD) was prepared by mixing small EVs with doxorubicin (DOX). PexD and an anti-PD-L1 monoclonal antibody (aPD-L1) were co-encapsulated in fibrin gel. The synergistic antitumour efficacy of the gel containing PexD and aPD-L1 was assessed both in vitro and in vivo. Herein, we developed an in situ-formed bioresponsive gel combined with chemoimmunotherapeutic agents as a drug reservoir that could effectively inhibit both local tumour recurrence and tumour metastasis. In comparison with a DOX solution, PexD could better bind to tumour cells, induce more tumour immunogenic cell death (ICD) and promote a stronger antitumour immune response. PexD could enter the blood circulation through damaged blood vessels to track and eliminate CTCs. The concurrent release of aPD-L1 at the tumour site could impair the PD-1/PD-L1 pathway and restore the tumour-killing effect of cytotoxic T cells. This chemoimmunotherapeutic strategy triggered relatively strong T cell immune responses, significantly improving the tumour immune microenvironment. Our findings indicated that the immunotherapeutic fibrin gel could “awaken” the host innate immune system to inhibit both local tumour recurrence post-surgery and metastatic potential, thus, it could serve as a promising approach to prevent tumour recurrence.
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         Recurrence
         Metastasis
         Drug reservoir
         Platelet-derived small EVs
         PD-L1
         Biotechnology
         Nanotechnology
         Molecular Medicine
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            name:Shenyang Pharmaceutical University
            address:
               name:School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China
               type:PostalAddress
            type:Organization
      name:Jin Sun
      url:http://orcid.org/0000-0001-5470-1599
      affiliation:
            name:Shenyang Pharmaceutical University
            address:
               name:Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China
      name:Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China
      name:Multi-Scale Robotics Lab (MSRL), Institute of Robotics & Intelligent Systems (IRIS), ETH Zurich, Zurich, Switzerland
      name:Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China
      name:Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China
      name:Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China
      name:Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China
      name:Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China
      name:Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China
      name:Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, China
      name:Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China
      name:Department of Biomedical Engineering, School of Medical Devices, Shenyang Pharmaceutical University, Shenyang, China
      name:School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China
      name:Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China

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