Sulfatide-tenascin interaction mediates binding to the extracellular matrix and endocytic uptake of liposomes in glioma cells.
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.
Shao
K
K
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 21 Lower Kent Ridge Road, Singapore, 119077, Singapore.
Hou
Q
Q
Go
M L
ML
Duan
W
W
Cheung
N S
NS
Feng
S-S
SS
Wong
K P
KP
Yoram
A
A
Zhang
W
W
Huang
Z
Z
Li
Q-T
QT
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
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