Efficient delivery of plasmid DNA using cholesterol-based cationic lipids containing polyamines and ether linkages

Cationic liposomes are broadly used as non-viral vectors to deliver genetic materials that can be used to treat various diseases including cancer. To circumvent problems associated with cationic liposome-mediated delivery systems such as low transfection efficiency and serum-induced inhibition, chol...

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Bibliographic Details
Published in:International journal of molecular sciences 2014-04, Vol.15 (5), p.7293-7312
Main Authors: Kim, Bieong-Kil, Seu, Young-Bae, Bae, Yun-Ui, Kwak, Tae-Won, Kang, Hyungu, Moon, Ik-Jae, Hwang, Guen-Bae, Park, So-Young, Doh, Kyung-Oh
Format: Article
Language:English
Subjects:
Animals
cationic lipids
Cations - chemistry
Cell Line
Cercopithecus aethiops
Cholesterol
Cholesterol - analogs & derivatives
COS Cells
cyanoethylation
Deoxyribonucleic acid
DNA
DNA - administration & dosage
DNA - genetics
gene delivery
Gene therapy
Humans
Lipids
Liposomes - chemistry
macropinocytosis
Plasmids
Plasmids - administration & dosage
Plasmids - genetics
Transfection
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Summary:Cationic liposomes are broadly used as non-viral vectors to deliver genetic materials that can be used to treat various diseases including cancer. To circumvent problems associated with cationic liposome-mediated delivery systems such as low transfection efficiency and serum-induced inhibition, cholesterol-based cationic lipids have been synthesized that resist the effects of serum. The introduction of an ether-type linkage and extension of the aminopropyl head group on the cholesterol backbone increased the transfection efficiency and DNA binding affinity compared to a carbamoyl-type linkage and a mono aminopropyl head group, respectively. Under optimal conditions, each liposome formulation showed higher transfection efficiency in AGS and Huh-7 cells than commercially available cationic liposomes, particularly in the presence of serum. The following molecular structures were found to have a positive effect on transfection properties: (i) extended aminopropyl head groups for a strong binding affinity to plasmid DNA; (ii) an ether linkage that favors electrostatic binding to plasmid DNA; and (iii) a cholesterol backbone for serum resistance.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms15057293