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Membrane-Fusion-Mediated Multiplex Engineering of Tumor Cell Surface Glycans for Enhanced NK Cell Therapy.
- Source :
-
Advanced materials (Deerfield Beach, Fla.) [Adv Mater] 2023 Apr; Vol. 35 (14), pp. e2206989. Date of Electronic Publication: 2023 Jan 15. - Publication Year :
- 2023
-
Abstract
- Natural killer (NK) cell therapies show potential for tumor treatment but are immunologically resisted by the overexpressed immunosuppressing tumor cell surface glycans. To reverse this glycan-mediated immunosuppression, the surface NK-inhibitory glycan expressions need to be downregulated and NK-activating glycan levels should be elevated synchronously with optimal efficiency. Here, a core-shell membrane-fusogenic liposome (MFL) is designed to simultaneously achieve the physical modification of NK-activating glycans and biological inhibition of immunosuppressing glycans on the tumor cell surface via a membrane-fusion manner. Loaded into a tumor-microenvironment-triggered-degradable thermosensitive hydrogel, MFLs could be conveniently injected and controllably released into local tumor. Through fusion with tumor cell membrane, the released MFLs could simultaneously deliver sialyltransferase-inhibitor-loaded core into cytoplasm, and anchor NK-activating-glycan-modified shell onto tumor surface. This spatially-differential distribution of core and shell in one cell ensures the effective inhibition of intracellular sialyltransferase to downregulate immunosuppressing sialic acid, and direct presentation of NK-activating Lewis X trisaccharide (LeX) on tumor surface simultaneously. Consequentially, the sialic acid-caused immunosuppression of tumor surface is reprogrammed to be LeX-induced NK activation, resulting in sensitive susceptibility to NK-cell-mediated recognition and lysis for improved tumor elimination. This MFL provides a novel platform for multiplex cell engineering and personalized regulation of intercellular interactions for enhanced cancer immunotherapy.<br /> (© 2023 Wiley-VCH GmbH.)
Details
- Language :
- English
- ISSN :
- 1521-4095
- Volume :
- 35
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- Advanced materials (Deerfield Beach, Fla.)
- Publication Type :
- Academic Journal
- Accession number :
- 36566024
- Full Text :
- https://doi.org/10.1002/adma.202206989