Natural killer cell encapsulation in core-shell proteinic adhesive microcapsules for persistent and localized release of cytotoxic factors.

Natural killer (NK) cells have attracted considerable interest as a readily available product for cancer immunotherapy, particularly because of their low incidence of graft-versus-host disease in allogeneic settings. Nevertheless, the effectiveness of this strategy is often compromised by the limited in vivo persistence of NK cells and suboptimal targeting efficiency toward malignant tissues. In this study, we engineered adhesive microcapsules laden with NK cells, comprising an aqueous core that houses NK cells and an outer shell fabricated from bioengineered mussel adhesive protein (MAP) for persistent, localized NK cell-based cancer immunotherapy. These MAP-encased NK cell microcapsules (MAP@NK MCs), prepared using droplet microfluidics, demonstrated effective encapsulation and facilitated NK cell proliferation. This can be attributed to the favorable aqueous environment for immune cells encapsulated in the core and the nutrient-transporting semipermeable nature of the MAP shell. Moreover, the MAP@NK MCs exhibited robust adhesion to biological tissues, thereby enhancing their in vivo persistence and enabling sustained release of cytotoxic soluble factors from the encapsulated NK cells, resulting in effective in vitro and ex vivo anticancer outcomes. Thus, we contend that MAP@NK MCs, featuring immune cell-favorable aqueous microenvironments and robust wet adhesion properties, offer significant potential in NK cell-based cancer treatment modalities.