Lipid-based polymeric biomaterial-mediated ex vivo natural killer cell surface engineering

Natural killer (NK) cell-based immunotherapy has gained significant attention due to its ability to selectively recognize and eliminate cancer cells through immunological synapse formation while sparing normal cells. However, the therapeutic efficacy of NK cells against solid tumors remains limited, primarily due to insufficient tumor-specific targeting ligands. Although chimeric antigen receptor (CAR)-engineered NK cell therapy has been developed to address this challenge, its clinical translation is hindered by challenges like high cost, low transfection efficiency, and concerns associated with genetic modification. As an alternative, biomaterial-based NK cell surface engineering has emerged as a promising strategy to enhance tumor-targeting capabilities, without altering the intrinsic properties of NK cells. In particular, lipid-based polymeric biomaterial platforms enable efficient ligand-receptor interactions, thereby enhancing NK cell-mediated tumor recognition and cytotoxicity. This review highlights recent advances in the lipid-based NK cell surface engineering platform, discussing its advantages over genetic modifications and its potential to improve the efficacy of NK cell-based cancer immunotherapy.