title: DNA complexing lipopolythiourea.
abstract: We present a neutral lipopolythiourea (DTTU) as a potential DNA-binding agent. Light scattering experiments showed that mixing a lipopolythiourea with dipalmitoylphosphatidylcholine (DPPC/DTTU) led to small particles with sizes ranging from 100 to 150 nm at optimum conditions. Setting a fixed DNA amount, an increasing amount of DTTU/DPPC or DPPC lipids was added. Particle size increased only with DTTU/DPPC, indicating that interaction occurred between the DTTU/DPPC particles and DNA. In the same way, only DTTU/DPPC limited the ethidium bromide accessibility to plasmid DNA. These data suggest that DTTU/DPPC liposomes associate to DNA, which was confirmed by agarose gel experiments. To prove the active part of the DTTU lipid itself in DNA compaction, pegoylated-lipid was used. Cholesterol-PEG(2000) alone was not able to condense DNA. In contrast, DTTU/PEG-cholesterol was able to retain plasmid DNA on an agarose gel. In vivo injection of DTTU/DPPC/complexes was studied. Circulation time increase for noncationic particles as compared to cationic. More obvious was the lack of nonspecific accumulation in the lung, where a gain of 3 to 40 fold was measured.
authors.affiliation: Laboratoire de Pharmacologie Chimique et Génétique CNRS-UMR 8115, INSERM-U640, ENSCP 11 rue Pierre et Marie Curie 75231 Paris Cedex 05, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Tranchant
authors.forename: Nathalie
authors.initials: N
authors.lastname: Mignet
authors.forename: Estelle
authors.initials: E
authors.lastname: Crozat
authors.forename: Jeanne
authors.initials: J
authors.lastname: Leblond
authors.forename: Christian
authors.initials: C
authors.lastname: Girard
authors.forename: Daniel
authors.initials: D
authors.lastname: Scherman
authors.forename: Jean
authors.initials: J
authors.lastname: Herscovici
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001682:Biological Availability; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy / Q000378:metabolism; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D008081:Liposomes; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D013890:Thiourea / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000378:metabolism*
chemical_list: D008081:Liposomes; D015060:1,2-Dipalmitoylphosphatidylcholine; D004247:DNA; D013890:Thiourea