TY - JOUR
T1 - Tailoring tumor-recognizable hyaluronic acid–lipid conjugates to enhance anticancer efficacies of surface-engineered natural killer cells
AU - Lee, Chae Eun
AU - Kim, Sungjun
AU - Park, Hee Won
AU - Lee, Wonjeong
AU - Jangid, Ashok Kumar
AU - Choi, Yonghyun
AU - Jeong, Woo Jin
AU - Kim, Kyobum
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - Natural killer (NK) cells have clinical advantages in adoptive cell therapy owing to their inherent anticancer efficacy and their ability to identify and eliminate malignant tumors. However, insufficient cancer-targeting ligands on NK cell surfaces often inhibit their immunotherapeutic performance, especially in immunosuppressive tumor microenvironment. To facilitate tumor recognition and subsequent 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 through hydrophobic interaction) conjugates for biomaterial-mediated ex vivo NK cell surface engineering. Among these major compartments (i.e., Lipid, PEG and HA), optimization of lipid anchors (in terms of chemical structure and intrinsic amphiphilicity) is the most important design parameter to modulate hydrophobic interaction with dynamic NK cell membranes. Here, three different lipid types including 1,2-dimyristoyl-sn-glycero-3-phosphati-dylethanolamine (C14:0), 1,2-distearoyl-sn-glycero-3-phosphatidylethanolamine (DSPE, C18:0), and cholesterol were evaluated to maximize membrane coating efficacy and associated anticancer performance of surface-engineered NK cells (HALipid-NK cells). Our results demonstrated that NK cells coated with HA-PEG-DSPE conjugates exhibited significantly enhanced anticancer efficacies toward MDA-MB-231 breast cancer cells without an off-target effect on human fibroblasts specifically via increased NK cell membrane coating efficacy and prolonged surface duration of HA onto NK cell surfaces, thereby improving HA-CD44 recognition. These results suggest that our HALipid-NK cells with tumor-recognizable HA-PEG-DSPE conjugates could be further utilized in various cancer immunotherapies. Graphical Abstract: [Figure not available: see fulltext.].
AB - Natural killer (NK) cells have clinical advantages in adoptive cell therapy owing to their inherent anticancer efficacy and their ability to identify and eliminate malignant tumors. However, insufficient cancer-targeting ligands on NK cell surfaces often inhibit their immunotherapeutic performance, especially in immunosuppressive tumor microenvironment. To facilitate tumor recognition and subsequent 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 through hydrophobic interaction) conjugates for biomaterial-mediated ex vivo NK cell surface engineering. Among these major compartments (i.e., Lipid, PEG and HA), optimization of lipid anchors (in terms of chemical structure and intrinsic amphiphilicity) is the most important design parameter to modulate hydrophobic interaction with dynamic NK cell membranes. Here, three different lipid types including 1,2-dimyristoyl-sn-glycero-3-phosphati-dylethanolamine (C14:0), 1,2-distearoyl-sn-glycero-3-phosphatidylethanolamine (DSPE, C18:0), and cholesterol were evaluated to maximize membrane coating efficacy and associated anticancer performance of surface-engineered NK cells (HALipid-NK cells). Our results demonstrated that NK cells coated with HA-PEG-DSPE conjugates exhibited significantly enhanced anticancer efficacies toward MDA-MB-231 breast cancer cells without an off-target effect on human fibroblasts specifically via increased NK cell membrane coating efficacy and prolonged surface duration of HA onto NK cell surfaces, thereby improving HA-CD44 recognition. These results suggest that our HALipid-NK cells with tumor-recognizable HA-PEG-DSPE conjugates could be further utilized in various cancer immunotherapies. Graphical Abstract: [Figure not available: see fulltext.].
KW - Ex vivo cell surface engineering
KW - Hyaluronic acid–Lipid conjugate
KW - Hydrophobic membrane interaction
KW - Lipid anchor
KW - Natural killer cell
UR - http://www.scopus.com/inward/record.url?scp=85179736715&partnerID=8YFLogxK
U2 - 10.1186/s40580-023-00406-1
DO - 10.1186/s40580-023-00406-1
M3 - Article
AN - SCOPUS:85179736715
SN - 2196-5404
VL - 10
JO - Nano Convergence
JF - Nano Convergence
IS - 1
M1 - 56
ER -