Linked Life Data

15456264

Source:http://linkedlifedata.com/resource/pubmed/id/15456264

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
2004-9-30
pubmed:abstractText
Cationic lipid-mediated gene transfection involves uptake of the lipid/DNA complexes via endocytosis, a cellular pathway characterized by a significant drop in pH. Thus, in the present study, we aimed to explore the impact on transfection efficiency of the inclusion of an acid-sensitive acylhydrazone function in the cationic lipid structure. We synthesized and evaluated the transfection properties of a series of four cationic steroid derivatives characterized by an acylhydrazone linkage connecting a guanidinium-based headgroup to a saturated cholestanone or an unsaturated cholest-4-enone hydrophobic domain. Acid-catalyzed hydrolysis was confirmed for all lipids, its rate being highest for those with a cholestanone moiety. The compound bis-guanidinium bis(2-aminoethyl)amine hydrazone (BGBH)-cholest-4-enone was found to mediate efficient gene transfection into various mammalian cell lines in vitro and into the mouse airways in vivo. In vitro transfection studies with BGBH-cholest-4-enone formulations also showed that incorporation of a degradable acylhydrazone bond led to low cytotoxicity and impacted the intracellular trafficking of the lipoplexes. Thus, our work allowed us to identify a cationic lipid structure with an acid-cleavable acylhydrazone linker capable of mediating efficient gene transfection in vitro and in vivo and it thereby provides a basis for further development of related acid-sensitive gene delivery systems.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
7
pubmed:volume
47
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5210-23
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Novel cationic lipids incorporating an acid-sensitive acylhydrazone linker: synthesis and transfection properties.
pubmed:affiliation
INSERM U458, Hôpital Robert Debré, AP-HP, 48 Boulevard Sérurier, 75019 Paris, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't