Lipopolythiourea Transfecting Agents: Lysine Thiourea Derivatives

Synthetic vectors represent an alternative to recombinant viruses for gene transfer. We have recently explored the transfection potential of a class of noncationic lipids bearing thiourea moieties as DNA-associating headgroups. The encouraging results obtained with lipopolythioureas derived from ser...

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Bibliographic Details
Published in:Bioconjugate chemistry 2008-01, Vol.19 (1), p.306-314
Main Authors: Leblond, Jeanne, Mignet, Nathalie, Largeau, Céline, Seguin, Johanne, Scherman, Daniel, Herscovici, Jean
Format: Article
Language:English
Subjects:
Animals
Chemical Sciences
DNA - metabolism
Gene expression
Injections
Life Sciences
Lipid Metabolism
Lipids
Lysine - administration & dosage
Lysine - blood
Lysine - chemistry
Lysine - metabolism
Mice
Organic chemistry
Pharmaceutical sciences
Proteins
Serum - metabolism
Studies
Thiourea - administration & dosage
Thiourea - blood
Thiourea - chemistry
Thiourea - metabolism
Toxicity
Transfection - methods
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Summary:Synthetic vectors represent an alternative to recombinant viruses for gene transfer. We have recently explored the transfection potential of a class of noncationic lipids bearing thiourea moieties as DNA-associating headgroups. The encouraging results obtained with lipopolythioureas derived from serinol prompted us to further investigate this family of vectors. In the present study, we considered the transfection properties of a series of derivatives based on a different thiourea polar headgroup bearing a lysine scaffold. The synthesis of these compounds could be readily achieved in three steps with good yields. We found that these lipopolythioureas (LPT) might be considered as alternative systems for gene transfection since their activity reached the same magnitude range as that of cationic vectors in the presence of serum. LPT with 14-carbon length chains appeared to be more efficient as a transfecting agent than the ones with shorter chains. Toxicity studies proved that the hydration film method led to particles well tolerated both by the cells in vitro and by the mice in vivo. The ability to induce gene expression in vivo was demonstrated by intratumoral injection. Finally, biodistribution studies showed that the quantity recovered in blood circulation, 2 h after systemic injection, was improved as compared to that in cationic lipids.
ISSN:1043-1802
1520-4812
DOI:10.1021/bc7001924