title: Effects of liposomal phospholipids and lipid transport-related protein on the intracellular fate of encapsulated doxorubicin.
abstract: We have previously reported the intracellular trafficking mechanism of liposomal phospholipids. In the present study, we investigated the effects of liposomal phospholipids on the intracellular trafficking of doxorubicin (DXR). In DXR-encapsulated liposomes, polyethylene glycol (PEG)-modified phospholipids have been widely used as one of the liposomal lipids. First, we investigated the intracellular trafficking mechanism of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy-PEG2000] (PEG2000-DSPE), and demonstrated that the intracellular trafficking pathways of phospholipids changed by PEG modification. Then, we evaluated the effects of liposomal DXR on the intracellular trafficking of liposomal phospholipids. Under the phosphatidylinositol transfer protein (PITP)-suppressing condition by siRNA treatment, the intracellular amounts of DSPC derived from DXR-encapsulated liposomes were larger than that from nonencapsulated liposomes. Moreover, following the effects of liposomal phospholipids on the intracellular amounts of DXR, the intracellular amounts of DXR were increased under the PITP-suppressing condition in DXR-encapsulated liposomes. We showed that intracellular DXR was associated with the complex of PITP and DSPC, and the extracellular efflux of DXR was enhanced by complex formation with PITP and DSPC.
authors.affiliation: Division of Drugs, National Institute of Health Sciences , 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Un
authors.forename: Kumiko
authors.initials: K
authors.lastname: Sakai-Kato
authors.forename: Toru
authors.initials: T
authors.lastname: Kawanishi
authors.forename: Haruhiro
authors.initials: H
authors.lastname: Okuda
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Goda
mesh_terms: D015153:Blotting, Western; D002214:Capsules / Q000737:chemistry; D004317:Doxorubicin / Q000378:metabolism*; D016503:Drug Delivery Systems; D006367:HeLa Cells; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D018613:Microscopy, Confocal; D008954:Models, Biological; D010743:Phospholipids / Q000737:chemistry*
chemical_list: D002214:Capsules; D008081:Liposomes; D010743:Phospholipids; D004317:Doxorubicin