NK cells are the first line of defense against infection and malignancy. Without prior sensitization, NK cells are able to recognize and destroy malignant cells. However, NK cell activation in solid tumors is still limited by the acidic condition, low oxygen level, and immunosuppressive mechanism of the solid tumor environment.
This study aimed to encapsulate NK cells in hydrogel microspheres to prevent the deterioration of NK cells activation under hypoxic condition in the tumor microenvironment (TME). We used alginate and gelatin, which have excellent biocompatibility and ease of crosslinking, and designed alginate-gelatin hydrogels with a diameter of 450~490 μm to allow sufficient diffusion of nutrients and oxygen inside. Alginate-gelatin hydrogel was generated using electrospray technology. The encapsulated NK cells showed proliferation and tumor-killing effect inside the biocompatible alginate-gelatin hydrogel even under normoxia. In addition, it showed a protective effect on cell viability under hypoxic condition, and NK cell-mediated tumor-killing effect was maintained under hypoxic condition compared to normoxia through the upregulation of GZMB and IFN-γ.
In summary, the encapsulation of NK cells with alginate-gelatin hydrogel microspheres showed that NK cells have a protective effect regarding cell viability and tumor-killing effect by preventing the inhibition of activation under hypoxia in TME.