DNA complexing lipopolythiourea.
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.
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Isabelle
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Laboratoire de Pharmacologie Chimique et Génétique CNRS-UMR 8115, INSERM-U640, ENSCP 11 rue Pierre et Marie Curie 75231 Paris Cedex 05, France.
Mignet
Nathalie
N
Crozat
Estelle
E
Leblond
Jeanne
J
Girard
Christian
C
Scherman
Daniel
D
Herscovici
Jean
J
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*
D008081:Liposomes; D015060:1,2-Dipalmitoylphosphatidylcholine; D004247:DNA; D013890:Thiourea