title: Intracellular drug delivery by sulfatide-mediated liposomes to gliomas.
abstract: We described here a liposomal carrier system in which the targeting ligand was sulfatide, a glycosphingolipid known to bind several extracellular matrix (ECM) glycoproteins whose expression was highly up-regulated in many tumors. In vitro experiments with human glioma cell lines demonstrated that robust intracellular uptake of the liposomes depended specifically on the presence of sulfatide as the key liposomal component. Significant amount of the liposomes remained largely intact in the cytoplasm for hours following their internalization. When anticancer drug doxorubicin (DOX) was encapsulated in such liposomes, most of the drug was preferably delivered into the cell nuclei to exert its cytotoxicity. Use of this drug delivery system to deliver DOX for treatment of tumor-bearing nude mice displayed much improved therapeutic effects over the free drug or the drug carried by polyethylene glycol (PEG)-grafted liposomes. Our results demonstrate a close link between effective intracellular uptake of the drug delivery system and its therapeutic outcome. Moreover, the sulfatide-containing liposomes (SCL) may represent an interesting ligand-targeted drug carrier for a wide spectrum of cancers in which sulfatide-binding ECM glycoproteins are expressed.
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Block MD7, 8 Medical Drive, Singapore.
authors.forename: Ke
authors.initials: K
authors.lastname: Shao
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Hou
authors.forename: Wei
authors.initials: W
authors.lastname: Duan
authors.forename: Mei Lin
authors.initials: ML
authors.lastname: Go
authors.forename: Kim Ping
authors.initials: KP
authors.lastname: Wong
authors.forename: Qiu-Tian
authors.initials: QT
authors.lastname: Li
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001932:Brain Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D008081:Liposomes; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D009368:Neoplasm Transplantation; D013433:Sulfoglycosphingolipids / Q000494:pharmacology*; D013534:Survival; D014183:Transplantation, Heterologous
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008081:Liposomes; D013433:Sulfoglycosphingolipids; D004317:Doxorubicin