Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 15, Issue 5, Pages 7293-7312Publisher
MDPI AG
DOI: 10.3390/ijms15057293
Keywords
cholesterol; cationic lipids; cyanoethylation; transfection; gene delivery; macropinocytosis
Funding
- National Research Foundation of Korea (NRF) grant - Korea government (MEST) [2005-0049417]
- Basic Science Research Program - Ministry of Education, Science and Technology [2011-0026282]
- Yeungnam University Research Grant [211-A-345-008]
- National Research Foundation of Korea [2005-0049417] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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.
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