이채은 (동국대학교)

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동국대학교

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Nano Converg., Dec 14 2023, 10 (1) 56 | https://doi.org/10.1186/s40580-023-00406-1 Tailoring tumor-recognizable hyaluronic acid-lipid conjugates to enhance anticancer efficacies of surface-engineered natural killer cells

Chae Eun Lee^1†, Sungjun Kim^1†, Hee Won Park¹, Wonjeong Lee¹, Ashok Kumar Jangid¹, Yonghyun Choi³, Woo‑Jin Jeong^2* and Kyobum Kim^1*

¹Department of Chemical & Biochemical Engineering, Dongguk University, Seoul 04620, Republic of Korea.

²Department of Biological Engineering, Inha University, Incheon 22212, Republic of Korea.

³Department of Chemical Science and Engineering, Tokyo Institute of Technology, Kanagawa 226‑8501, Japan.

^†Chae Eun Lee and Sungjun Kim contributed equally to this work.

^*Correspondence: Woo‑Jin Jeong, Kyobum Kim

Abstract

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.

논문정보

형식Research article
게재일2023년 12월 (BRIC 등록일 2023-12-19)
연구진국내(교신)+국외 연구진
분야 생명과학 > 생물공학

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