화학공학소재연구정보센터
Journal of the American Chemical Society, Vol.127, No.32, 11436-11441, 2005
Monomolecular DNA nanoparticles for intravenous delivery of genes
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 phosphaticlylserine, 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.