Abstract
The design, synthesis and biological evaluation of the cationic lipid gene delivery vectors based on cholesterol and natural amino acids lysine or histidine are described. Cationic liposomes composed of the newly synthesized cationic lipids 1a or 1b and neutral lipid DOPE (1,2-dioleoyl-l-α-glycero-3-phosphatidyl-ethanolamine) exhibited good transfection efficiency. pEGFP-N1 plasmid DNA was transferred into 293T cells by cationic liposomes formed from cationic lipids 1a and 1b, and the transfection activity of the cationic lipids was superior (1a) or parallel (1b) to that of the commercially available 3β-[N-(N',N'-dimethylaminoethyl)-carbamoyl] cholesterol (DC-Chol) derived from the same cholesterol backbone with different head groups. Combined with the results of agarose gel electrophoresis, transfection experiments with various molar ratios of the cationic lipids and DOPE and N/P (+/−) molar charge ratios, a more effective formulation was formed, which could lead to relatively high transfection efficiency. Cationic lipid 1a represents a potential agent for the liposome used in gene delivery due to low cytotoxicity and impressive gene transfection activity.
Highlights
Gene therapy plays an important role in the treatment of inherited and acquired diseases, such as cancer, cardiovascular diseases, AIDS and autoimmune disorders
Cationic lipids are based on a cholesterol backbone, where the cholesterol is linked to positive-charged basic amino acid residues via ether linked to the cholesterol backbone and amide linked to the amino acid (Figure 2)
Compound 4 was synthesized from natural cholesterol through three steps
Summary
Gene therapy plays an important role in the treatment of inherited and acquired diseases, such as cancer, cardiovascular diseases, AIDS and autoimmune disorders. The success of gene therapy relies on finding efficient and safe vectors for gene delivery [1,2,3,4]. Viral vectors are an efficient means for gene delivery, but some side effects, including immunogenicity and biological safety, limit application in clinical trials [5,6]. For these reasons, non-viral vectors, such as cationic lipids, cationic polymers and peptides, represent an attractive, alternative approach to gene delivery [7,8,9]. Liposomes based on cationic lipids have been favored for many potential advantages compared with other non-viral vectors, which, in general, exhibit excellent biocompatibility, low immunogenicity, low toxicity and large nucleic acid carrying capacity
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