Tailoring Tumor-Recognizable Hyaluronic acid–Lipid Conjugates to Enhance Anticancer Efficacies of Surface-Engineered Natural Killer Cells
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Natural killer (NK) cells have clinical advantages in adoptive cell therapy owing to their inherent anticancer efficacy. However, insufficient cancer-targeting ligands on NK cells often limit their performance in immunosuppressive environments. To facilitate anticancer function of NK cells, we developed hyaluronic acid (HA, ligands to target CD44 overexpressed onto cancer cells)-poly (ethylene glycol) (PEG, cytoplasmic penetration blocker)-Lipid (molecular anchor for NK cell membrane decoration via hydrophobic interaction) conjugates for biomaterial-mediated ex vivo NK cell surface engineering. Here, optimization of lipid anchor (in terms of chemical structure and intrinsic amphiphilicity) is the most important design parameter to modulate hydrophobic interaction with dynamic NK cell membranes. Among different types of lipid anchors, our results demonstrated that NK cells coated with HA-PEG-DSPE exhibited enhanced anticancer efficacy against tripe-negative breast cancer cell.