Synthesis and evaluation of a quaternary amino disulfide cationic lipid inplasmid DNA delivery

Citation
F. Tang et Ja. Hughes, Synthesis and evaluation of a quaternary amino disulfide cationic lipid inplasmid DNA delivery, STP PHARM S, 11(1), 2001, pp. 83-90
Citations number
27
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
STP PHARMA SCIENCES
ISSN journal
1157-1489 → ACNP
Volume
11
Issue
1
Year of publication
2001
Pages
83 - 90
Database
ISI
SICI code
1157-1489(200101/02)11:1<83:SAEOAQ>2.0.ZU;2-E
Abstract
A quaternary amino disulfide cationic lipid. N',N',N'-trimethylaminoethyl-1 '-cholesteryl-3.3'-dithiodipropionamide (QS3) and its non-disulfide analog (QN3) were synthesized, and used to deliver plasmid DNA in vitro. 3-(-[N-(N ',N'-dimethylaminoethanol) carbarmoyl] cholesterol (DC-Chol) cationic lipid was used as a structural control analog in transfection studied. The resul ts indicated 1,2 -dioleoyl-sn-glycero-3-phosphocholine (DOPC) was a superio r helper lipid than 1,2-dioleoyl phosphoethanolamine (DOPE) in liposome for mulations composed of DC-Chol/DOPC, QS3/DOPC, or QN3/DOPC in CHO but not in SKnSH cells. DOPC has rarely been reported to have helper functions in gen e delivery. In order to understand the helper functions of DOPC, we investi gated the effects of DOPE and DOPC on the structure of DNA/liposomes comple xes. In addition, cellular toxicity and cellular associated DNA were also e xamined. The data demonstrated that not only was endocytosis the major path way for plasmid DNA delivery by these liposome formulations, but also that DOPC containing formulations did not deliver more DNA to cells or help DNA escape from endosomes. We propose that other intracellular events, such as intracellular trafficking, might play a significant role in the enhancement of transgene expression by DOPC in CHO cells.