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

Abstract Cancer recurrence and metastasis after surgical resection is a vital reason of treatment failure. The modification of immune cells through implanted biomaterials is a promising postoperative immunotherapy. Herein, an injectable hydrogel scaffold loaded with engineered exosome mimetics that in vivo recruits and programs endogenous macrophages into M1 binding with anti‐CD47 antibody (M1‐aCD47 macrophages) for postoperative cancer immunotherapy is developed. Briefly, M1 macrophages‐derived exosome mimetics co‐modified with vesicular stomatitis virus glycoprotein (VSV‐G) and aCD47 (V‐M1EM‐aCD47) are encapsulated in injectable chitosan hydrogel. Such hydrogel recruits inherent macrophages in situ and releases V‐M1EM‐aCD47 that programs M2 to M1‐aCD47 macrophages. M1‐aCD47 macrophages own dual‐functions of tumor‐homing and enhanced phagocytosis. They can actively target to tumor cells for delivery of aCD47 that blocks the “don't eat me” signal, thereby promoting phagocytosis of macrophages to cancer cells. Furthermore, V‐M1EM‐aCD47 hydrogel implanted into resection site of 4T1 breast tumor inhibits tumor recurrence and metastasis by phagocytosis of M1‐aCD47 macrophages and T cell‐mediated immune responses. The findings demonstrate that biomaterials can be designed in vivo to program inherent macrophages, thereby activating the innate and adaptive immune systems for prevention of postoperative tumor recurrence and metastasis.