title: Intracellular trafficking mechanism of cationic phospholipids including cationic liposomes in HeLa cells.
abstract: The development of gene delivery methods is essential for the achievement of effective gene therapy. Elucidation of the intracellular transfer mechanism for cationic carriers is in progress, but there are few reports regarding the intracellular trafficking processes of the cationic phospholipids taken up into cells. In the present work, the trafficking processes of a cationic phospholipid (1,2-dioleoyl-3-trimethylammonium-propane, DOTAP) were investigated from intracellular uptake to extracellular efflux using cationic liposomes in vitro. Following intracellular transport of liposomes via endocytosis, DOTAP was localized in the endoplasmic reticulum, Golgi apparatus, and mitochondria. Moreover, the proteins involved in DOTAP intracellular trafficking and extracellular efflux were identified. In addition, helper lipids of cationic liposomes were found to partially affect this intracellulartrafficking. These findings might provide valuable information for designing cationic carriers and avoiding unexpected toxic side effects derived from cationic liposomal components.
authors: K
authors: K
authors: Un
authors: K
authors: K
authors: Sakai-Kato
authors: Y
authors: Y
authors: Goda
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D002412:Cations; D004563:Electrochemistry; D004705:Endocytosis; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism; D018014:Gene Transfer Techniques; D006056:Golgi Apparatus / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism*; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism; D009696:Nucleic Acids / Q000378:metabolism; D010316:Particle Size; D010713:Phosphatidylcholines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D034741:RNA, Small Interfering
chemical_list: D018528:ATP-Binding Cassette Transporters; D002412:Cations; D005229:Fatty Acids, Monounsaturated; D008081:Liposomes; D009696:Nucleic Acids; D010713:Phosphatidylcholines; D010743:Phospholipids; D000644:Quaternary Ammonium Compounds; D034741:RNA, Small Interfering; C017251:1,2-oleoylphosphatidylcholine; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane