title: Targeted liposomes to deliver DNA to cells expressing 5-HT receptors.
abstract: Cell targeted delivery of drugs, including nucleic acids, is known to enhance the therapeutic potential of free drugs. We used serotonin (5-HT) as the targeting ligand to deliver plasmid DNA to cells specifically expressing 5-HT receptor. Our liposomal formulation includes the 5-HT conjugated targeting lipid, a cationic lipid and cholesterol. DNA-binding studies indicate that the targeting 5-HT-lipid binds DNA efficiently. The formulation was tested and found to efficiently deliver DNA into CHO cells stably expressing the human serotonin(1A) receptor (CHO-5-HT(1A)R) compared to control CHO cells. Liposomes without the 5-HT moiety were less efficient in both cell lines. Similar enhancement in transfection efficiency was also observed in human neuroblastoma IMR32 and hepatocellular carcinoma (HepG2) cells. Cell uptake studies using CHO-5-HT(1A)R cells by flow cytometry and confocal microscopy clearly indicated that the targeting liposomes through 5-HT moiety may have a direct role in increasing the cellular uptake of DNA-lipid complexes. To our knowledge this is the first report that demonstrates receptor-targeted nucleic acid delivery into cells expressing 5-HT receptor.
authors.affiliation: Centre for Cellular and Molecular Biology (A Council of Scientific and Industrial Research Laboratory), Uppal Road, Hyderabad 500007, India.
authors.forename: Vijaya
authors.initials: V
authors.lastname: Gopal
authors.forename: Jennifer
authors.initials: J
authors.lastname: Xavier
authors.forename: Gulam Hassan
authors.initials: GH
authors.lastname: Dar
authors.forename: Md
authors.initials: M
authors.lastname: Jafurulla
authors.forename: Amitabha
authors.initials: A
authors.lastname: Chattopadhyay
authors.forename: N Madhusudhana
authors.initials: NM
authors.lastname: Rao
mesh_terms: D000818:Animals; D016466:CHO Cells; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000008:administration & dosage*; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D056945:Hep G2 Cells; D006801:Humans; D008024:Ligands; D008081:Liposomes; D008113:Liver Neoplasms / Q000378:metabolism; D018613:Microscopy, Confocal; D009447:Neuroblastoma / Q000378:metabolism; D010957:Plasmids; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012701:Serotonin / Q000008:administration & dosage* / Q000378:metabolism; D014162:Transfection
chemical_list: D008024:Ligands; D008081:Liposomes; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D004247:DNA