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A Twindrive Precise Delivery System of Platelet-Neutrophil Hybrid Membrane Regulates Macrophage Combined with CD47 Blocking for Postoperative Immunotherapy

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    A Twindrive Precise Delivery System of Platelet-Neutrophil Hybrid Membrane Regulates Macrophage Combined with CD47 Blocking for Postoperative Immunotherapy
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    • Shupei Sheng
      Shupei Sheng
      Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, PR China
      More by Shupei Sheng
    • Limin Jin
      Limin Jin
      Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, PR China
      More by Limin Jin
    • Yan Zhang
      Yan Zhang
      Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, PR China
      More by Yan Zhang
    • Weiting Sun
      Weiting Sun
      Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, PR China
      More by Weiting Sun
    • Lin Mei
      Lin Mei
      Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, PR China
      More by Lin Mei
      Orcidhttps://orcid.org/0000-0001-6503-5149
    • Dunwan Zhu*
      Dunwan Zhu
      Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, PR China
      *Email: [email protected] (D. Zhu).
      More by Dunwan Zhu
      Orcidhttps://orcid.org/0000-0003-2401-3001
    • Xia Dong*
      Xia Dong
      Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, PR China
      *Email:[email protected] (X. Dong).
      More by Xia Dong
    • Feng Lv*
      Feng Lv
      Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, PR China
      *Email:[email protected] (F. Lv).
      More by Feng Lv
      Orcidhttps://orcid.org/0000-0002-0583-1810
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    ACS Nano

    Cite this: ACS Nano 2024, 18, 6, 4981–4992
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    https://doi.org/10.1021/acsnano.3c10862
    Published January 9, 2024
    Copyright © 2024 American Chemical Society
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    Abstract

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    During wound healing after cancer surgery, platelets, neutrophils, and macrophages accumulate at the wound site and induce important pathophysiological features. Utilizing these pathophysiological features, the development of targeted delivery systems for postoperative tumor immunotherapy is an important strategy. Herein, a twindrive precise delivery system of hybrid membrane combined with CD47 blocking is developed for targeted delivery and targeted regulation to induce postoperative immunotherapy. The precise delivery system consists of IR820-modified platelet-neutrophil hybrid membranes loaded with R848 nanoparticles. Based on the pathological characteristics of platelet aggregation and neutrophil tendency caused by the wound inflammatory microenvironment after tumor surgery, the twindrive delivery system could achieve targeted delivery and targeted regulation of immune drugs to tumor sites. After precise delivery guided by fluorescence imaging, R848 is targeted to reprogram M2 macrophages into M1 macrophages, stimulate dendritic cell maturation as an adjuvant, and then activate T cell immunity. R848 polarization and CD47 blockade together enhanced the phagocytosis function of macrophages, which combined with T cell-mediated cellular immune response to finally effectively inhibit postsurgical tumor recurrence, metastasis, and prolonged survival time. It develops a targeted delivery and regulatory system for cell-specific responses to the pathophysiological features of wound healing for postoperative immunotherapy.

    Copyright © 2024 American Chemical Society

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    Supporting Information

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsnano.3c10862.

    • Materials, cells, animal information, characterization of of RNP@PNM-IR, Western blotting, uptake mechanism, ELISA Assay, cells staining, flow cytometry for immune cell analysis, specific lysis assay, and some data (PDF)

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    ACS Nano

    Cite this: ACS Nano 2024, 18, 6, 4981–4992
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acsnano.3c10862
    Published January 9, 2024
    Copyright © 2024 American Chemical Society
    Request reuse permissions

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