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Int. J. Mol. Sci. 2014, 15(5), 7293-7312; doi:10.3390/ijms15057293

Efficient Delivery of Plasmid DNA Using Cholesterol-Based Cationic Lipids Containing Polyamines and Ether Linkages

1 School of Life Sciences & Biotechnology, Kyungpook National University, 1370 Sangyeokdong, Bookgu, Daegu 702-701, Korea 2 Department of Physiology, Yeungnam University College of Medicine, 317-1 Daemyungdong, Daegu 705-717, Korea 3 WelGENE Inc., 71B-4L, Hightech Sector 2, Sungseo Industrial Park 3, Dalseogu, Daegu 704-230, Korea These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 27 January 2014 / Revised: 24 March 2014 / Accepted: 10 April 2014 / Published: 28 April 2014
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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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.
Keywords: cholesterol; cationic lipids; cyanoethylation; transfection; gene delivery; macropinocytosis cholesterol; cationic lipids; cyanoethylation; transfection; gene delivery; macropinocytosis
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Kim, B.-K.; Seu, Y.-B.; Bae, Y.-U.; Kwak, T.-W.; Kang, H.; Moon, I.-J.; Hwang, G.-B.; Park, S.-Y.; Doh, K.-O. Efficient Delivery of Plasmid DNA Using Cholesterol-Based Cationic Lipids Containing Polyamines and Ether Linkages. Int. J. Mol. Sci. 2014, 15, 7293-7312.

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