Artificial Natural Killer Cells for Specific Tumor Inhibition and Renegade Macrophage Re‐Education

Abstract Natural killer (NK) cells can not only recognize and eliminate abnormal cells but also recruit and re‐educate immune cells to protect the host. However, the functions of NK cells are often limited in the immunosuppressive tumor microenvironment (TME). Here, artificial NK cells (designated as aNK) with minor limitations of TME for specific tumor killing and renegade macrophage re‐education are created. The red blood cell membrane (RBCM) cloaks perfluorohexane (PFC) and glucose oxidase (GOX) to construct the aNK. The aNK can directly kill tumor cells by exhausting glucose and generating hydrogen peroxide (H₂O₂). The generated H₂O₂ is also similar to cytokines and chemokines for recruiting immune cells and re‐educating survived macrophages to attack tumor cells. In addition, the oxygen‐carried PFC can strengthen the catalytic reaction of GOX and normalize the hypoxic TME. In vitro and in vivo experiments display that aNK with slight TME limitations exhibit efficient tumor inhibition and immune activation. The aNK will provide a new sight to treat tumor as the supplement of aggressive NK cells.