Effects of Liposomal Phospholipids and Lipid Transport-Related Protein on the Intracellular Fate of Encapsulated Doxorubicin

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 phosph...

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Bibliographic Details
Published in:Molecular pharmaceutics 2014-02, Vol.11 (2), p.560-567
Main Authors: Un, Keita, Sakai-Kato, Kumiko, Kawanishi, Toru, Okuda, Haruhiro, Goda, Yukihiro
Format: Article
Language:English
Subjects:
Blotting, Western
Capsules - chemistry
Doxorubicin - metabolism
Drug Delivery Systems
HeLa Cells
Humans
Liposomes - chemistry
Microscopy, Confocal
Models, Biological
Phospholipids - chemistry
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Summary: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.
ISSN:1543-8384
1543-8392
DOI:10.1021/mp400505a