title: pH-sensitive liposomes are efficient carriers for endoplasmic reticulum-targeted drugs in mouse melanoma cells.
abstract: Tyrosinase, the key enzyme of melanin biosynthesis, is inactivated in melanoma cells following the incubation with the imino-sugar N-butyldeoxynojirimycin, an inhibitor of the endoplasmic reticulum N-glycosylation processing. We have previously shown that tyrosinase inhibition requires high NB-DNJ concentrations, suggesting an inefficient cellular uptake of the drug. Here we show that the use of pH-sensitive liposomes composed of dioleoylphosphatidylethanolamine and cholesteryl hemisuccinate for the delivery of NB-DNJ reduced the required dose for tyrosinase inhibition by a factor of 1000. The results indicate that these pH-sensitive liposomes are efficient carriers for imino-sugars delivery in the endoplasmic reticulum of mammalian cells.
authors.affiliation: Institute of Biochemistry of the Romanian Academy, Splaiul Independentei 296, 77700 Bucharest, Romania.
authors.forename: Gertrude-E
authors.initials: GE
authors.lastname: Costin
authors.forename: Mihaela
authors.initials: M
authors.lastname: Trif
authors.forename: Norica
authors.initials: N
authors.lastname: Nichita
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Dwek
authors.forename: Stefana M
authors.initials: SM
authors.lastname: Petrescu
mesh_terms: D017485:1-Deoxynojirimycin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008081:Liposomes; D008545:Melanoma; D051379:Mice; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D010858:Pigmentation / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D004791:Enzyme Inhibitors; D008081:Liposomes; D017485:1-Deoxynojirimycin; C059896:miglustat; D014442:Monophenol Monooxygenase