Injectable Scaffolds for In Vivo Programmed Macrophages Manufacture and Postoperative Cancer Immunotherapy

Xiaodan Wu; Zhenyu Zhong; Yan LiYifan WangYaping TianXulong LiuXin ZhangWeiyong TaoJianglin WangYingying DuShengmin Zhang

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Injectable Scaffolds for In Vivo Programmed Macrophages Manufacture and Postoperative Cancer Immunotherapy

机译：Injectable Scaffolds for In Vivo Programmed Macrophages Manufacture and Postoperative Cancer Immunotherapy

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Cancer recurrence and metastasis after surgical resection is a vital reasonof treatment failure. The modification of immune cells through implantedbiomaterials is a promising postoperative immunotherapy. Herein, aninjectable hydrogel scaffold loaded with engineered exosome mimetics thatin vivo recruits and programs endogenous macrophages into M1 bindingwith anti-CD47 antibody (M1-aCD47 macrophages) for postoperative cancerimmunotherapy is developed. Briefly, M1 macrophages-derived exosomemimetics co-modified with vesicular stomatitis virus glycoprotein (VSV-G)and aCD47 (V-M1EM-aCD47) are encapsulated in injectable chitosanhydrogel. Such hydrogel recruits inherent macrophages in situ and releasesV-M1EM-aCD47 that programs M2 to M1-aCD47 macrophages. M1-aCD47macrophages own dual-functions of tumor-homing and enhanced phagocytosis.They can actively target to tumor cells for delivery of aCD47 thatblocks the “don’t eat me” signal, thereby promoting phagocytosis of macrophagesto cancer cells. Furthermore, V-M1EM-aCD47 hydrogel implantedinto resection site of 4T1 breast tumor inhibits tumor recurrence andmetastasis by phagocytosis of M1-aCD47 macrophages and T cell-mediatedimmune responses. The findings demonstrate that biomaterials can bedesigned in vivo to program inherent macrophages, thereby activating theinnate and adaptive immune systems for prevention of postoperative tumorrecurrence and metastasis.

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来源
《Advanced functional materials》 |2023年第26期|2300058.1-2300058.14|共14页
作者
Xiaodan Wu; Zhenyu Zhong; Yan LiYifan WangYaping TianXulong LiuXin ZhangWeiyong TaoJianglin WangYingying DuShengmin Zhang;
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作者单位

Department of Biomedical EngineeringHuazhong University of Science and TechnologyWuhan 430074, China,Advanced Biomaterials and Tissue Engineering CenterHuazhong University of Science and TechnologyWuhan 430074, China;

Department of Biomedical EngineeringHuazhong University of Science and TechnologyWuhan 430074, China,Advanced Biomaterials and Tissue Engineering CenterHuazhong University of Science and TechnologyWuhan 430074, China,NMPA Research Base of Regulatory Scien;

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正文语种英语
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cancer immunotherapy; exosome mimetics; injectable scaffolds; tumor targeting; vesicular stomatitis virus glycoprotein;

Injectable Scaffolds for In Vivo Programmed Macrophages Manufacture and Postoperative Cancer Immunotherapy

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