pH-sensitive liposomes are efficient carriers for endoplasmic reticulum-targeted drugs in mouse melanoma cells

• Published in: Biochemical and biophysical research communications Vol. 293; no. 3; pp. 918 - 923
• Main Authors: Costin, Gertrude-E, Trif, Mihaela, Nichita, Norica, Dwek, Raymond A, Petrescu, Stefana M
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.05.2002
• Subjects: 1-Deoxynojirimycin - administration & dosage; 1-Deoxynojirimycin - analogs & derivatives; 1-Deoxynojirimycin - metabolism; Animals; Dose-Response Relationship, Drug; Drug delivery; Drug Delivery Systems; Endoplasmic Reticulum - drug effects; Endoplasmic Reticulum - enzymology; Enzyme Inhibitors - administration & dosage; Enzyme Inhibitors - metabolism; Hydrogen-Ion Concentration; Kinetics; Liposomes; Melanoma; Mice; Monophenol Monooxygenase - metabolism; Mouse melanoma cell line; N-Butyldeoxynojirimycin; pH-sensitive liposomes; Pigmentation - drug effects; Tumor Cells, Cultured; Tyrosinase; Mouse melanoma cell line; Drug delivery; N-Butyldeoxynojirimycin; pH-sensitive liposomes; Tyrosinase
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/S0006-291X(02)00317-0

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.