High Transfection Efficiency of Cationic Lipids with Asymmetric Acyl–Cholesteryl Hydrophobic Tails

Abstract

The ability of a nonviral gene delivery system to overcome extra- and intracellular barriers is a critical issue for the future clinical applications of gene therapy. In recent years much effort has been focused on the development of a variety of DNA carriers, and cationic liposomes have become the most common nonviral gene delivery system. One hundred and eighty novel cationic lipids with asymmetric acyl-cholesteryl hydrophobic tails were synthesized by parallel solid-phase chemistry. The liposomes were prepared and gel retardation assays were used to study the binding efficiency between the prepared liposome and the DNA. Transfection efficiencies of the lipids were evaluated against various mammalian cells, such as human embryonic kidney (HEK293), human cervical adenocarcinoma (HeLa), canine osteosarcoma (D17), colorectal adenocarcinoma (COLO 205), and human prostate adenocarcinoma (PC3) cells. The lipids with an acyl portion at the terminal part of the polyamine backbone exhibited higher transfection efficiency than those with the acyl portion as an internal part of the backbone. These compounds also showed higher transfection efficiency and lower cytotoxicity than the commercially available agents, Effectene, DOTAP, and DC-Chol.

Synergistic Effect of Cationic Lipids with Different Polarheads, Central Core Structures and Hydrophobic Tails on Gene Transfection Efficiency

“…The transfection efficiency of the cationic liposome also depends on the cationic lipisomes/DNA ratio as previously reported by our group 19,33,34) and others. [35][36][37] To find out the optimal liposomes/DNA ratio, transfection experiments were performed against HEK293 cells by using mixture lipids/ DOPE ratio of 1 : 1.…”

“…Most of cationic liposomes including many commercially available transfection reagents which exhibited high transfection activity in the absence of serum lost their efficiency when transfected in the presence of serum. 34,38) In order to investigate the effect of serum on gene transfection efficiencies of mixture lipids, transfection experiments with our optimized lipid formulations were therefore performed in the presence of 10, 20, 30 and 40% serum. The results are shown in Fig.…”

“…19,33,34) To evaluate the transfection efficiency of these mixture lipids toward the different cell lines, human breast adenocarcinoma (MCF-7) and cervical epithelial adenocarcinoma (HeLa) cells, the experiments were performed by using optimum condition under serum-free conditions. The transfection efficiency of mixture lip- ids was compared with the commercially available transfection agent, Lipofectamine 2000, which was calculated as 100%.…”

Biotinylated Cyclen‐Contained Cationic Lipids as Non‐Viral Gene Delivery Vectors

“…Cationic lipids are amphiphilic organic molecules and generally consist of a positively charged hydrophilic polar head group and a non‐polar hydrophobic tail, and the two moieties are always tethered via a linker with special chemical bonds such as ether, ester, amide group, and carbamate, etc. . The structure of cationic lipids is significant for the transfection efficiency of cationic liposomes.…”

“…As a result, carbamate‐linked lipids have been used in gene delivery systems to achieve high delivery efficiency with low cytotoxicity . In addition, cationic lipidic molecules with asymmetric dihydrophobic tails were also reported to have possibly superior gene delivery ability .…”