title: Sulfatide-tenascin interaction mediates binding to the extracellular matrix and endocytic uptake of liposomes in glioma cells.
abstract: Tenascin-C is an extracellular matrix glycoprotein, whose expression is highly restricted in normal adult tissues, but markedly up-regulated in a range of tumors, and therefore serves as a potential receptor for targeted anticancer drug or gene delivery. We describe here a liposomal carrier system in which the targeting ligand is sulfatide. Experiments with tenascin-C-expressing glioma cells demonstrated that binding of liposomes to the extracellular matrix relied essentially on the sulfatide-tenascin-C interaction. Following binding to the extracellular matrix, the sulfatide-containing liposomes were internalized via both caveolae/lipid raft- and clathrin-dependent pathways, which would ensure direct cytoplasmic release of the cargoes carried in the liposomes. Such natural lipid-guided intracellular delivery targeting at the extracellular matrix glycoproteins of tumor cells thus opens a new direction for development of more effective anticancer chemotherapeutics in future.
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 21 Lower Kent Ridge Road, Singapore, 119077, Singapore.
authors.forename: K
authors.initials: K
authors.lastname: Shao
authors.forename: Q
authors.initials: Q
authors.lastname: Hou
authors.forename: M L
authors.initials: ML
authors.lastname: Go
authors.forename: W
authors.initials: W
authors.lastname: Duan
authors.forename: N S
authors.initials: NS
authors.lastname: Cheung
authors.forename: S-S
authors.initials: SS
authors.lastname: Feng
authors.forename: K P
authors.initials: KP
authors.lastname: Wong
authors.forename: A
authors.initials: A
authors.lastname: Yoram
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.forename: Z
authors.initials: Z
authors.lastname: Huang
authors.forename: Q-T
authors.initials: QT
authors.lastname: Li
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000906:Antibodies / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology; D002966:Clathrin / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005910:Glioma / Q000473:pathology*; D006801:Humans; D008081:Liposomes / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism; D013110:Sphingosine / Q000494:pharmacology; D013395:Sucrose / Q000494:pharmacology; D013433:Sulfoglycosphingolipids / Q000378:metabolism*; D019063:Tenascin / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000494:pharmacology; D047392:beta-Cyclodextrins / Q000494:pharmacology
chemical_list: D000906:Antibodies; D002966:Clathrin; D008081:Liposomes; D034741:RNA, Small Interfering; D013433:Sulfoglycosphingolipids; D019063:Tenascin; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D013395:Sucrose; D010738:Type C Phospholipases; D002117:Calcitriol; D013110:Sphingosine