Abstract
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.
Highlights
Successful transfer of genetic material including plasmids, antisense and decoy oligonucleotides, and siRNA is a significant issue in the field of gene therapy [1]
We focused on the development and application of cationic liposome delivery systems that can increase serum stability and transfection efficiency based on our preliminary data [17]
To compare ether synthesized by cyanoethylation and carbamoyl linkages on the cholesterol backbone, we synthesized lipid A (Figure 1), which contained a carbamoyl-linked propylamine head that was synthesized from cholesteryl chloroformate, using the methods described by Tsutomu et al [31]
Summary
Successful transfer of genetic material including plasmids, antisense and decoy oligonucleotides, and siRNA is a significant issue in the field of gene therapy [1]. Genetic material is degraded by nucleases and is ineffectively delivered into cells [2]. The development of safe and effective vectors for delivery into cells is needed. Non-viral vectors can deliver diverse chemical agents and nucleic acids. Non-viral systems are more favorable in the field of cancer therapy, and several clinical trials have been performed using liposomes [7,8]. Of the available non-viral vectors, cationic lipids have been the most extensively studied. The structure of cationic lipids generally comprises a cationic head group attached to a hydrophobic domain by a linker [9]
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