Monomolecular DNA nanoparticles for intravenous delivery of genes.
Fiche publication
Date publication
août 2005
Auteurs
Membres identifiés du Cancéropôle Est :
Dr ZUBER Guy
Tous les auteurs :
Chittimalla C, Zammut-Italiano L, Zuber G, Behr JP
Lien Pubmed
Résumé
Delivery is the major obstacle to success of nucleic-acid-based therapies. We have neutralized DNA with a cationic detergent (C12CCP) obtained by amide bond formation between dodecanoic acid, cysteinyl-cysteine, and diaminopropane. Subsequent detergent polymerization by formation of intermolecular disulfide bonds within the condensed plasmid DNA leads to 32-nm-large neutral particles. (C12CCP)n/DNA complexes are more stable than those formed with other gene delivery agents toward exchange with extracellular polyanions such as glycosaminoglycans. Yet exposure to phosphatidylserine, an ubiquitous intracellular anionic lipid, still releases DNA from the complexes for transcription of the carried gene. Pharmacokinetics and biodistribution in mice showed that 25% of the complexes were still circulating after 30 min (2% for other cationic lipid vectors) in a form essentially not bound to blood cells. Altogether, straightforward control over size and surface charge, stability toward aggregation or exchange, and favorable pharmacokinetics make these complexes attractive vehicles for reaching tumor metastases after injection in the blood circulation.
Référence
J Am Chem Soc. 2005 Aug 17;127(32):11436-41.