A review on cationic lipids with different linkers for gene delivery.

Cationic lipids have become known as one of the most versatile tools for the delivery of DNA, RNA and many other therapeutic molecules, and are especially attractive because they can be easily designed, synthesized and characterized. Most of cationic lipids share the common structure of cationic head groups and hydrophobic portions with linker bonds between both domains. The linker bond is an important determinant of the chemical stability and biodegradability of cationic lipid, and further governs its transfection efficiency and cytotoxicity. Based on the structures of linker bonds, they can be grouped into many types, such as ether, ester, amide, carbamate, disulfide, urea, acylhydrazone, phosphate, and other unusual types (carnitine, vinyl ether, ketal, glutamic acid, aspartic acid, malonic acid diamide and dihydroxybenzene). This review summarizes some research results concerning the nature (such as the structure and orientation of linker groups) and density (such as the spacing and the number of linker groups) of linker bond for improving the chemical stability, biodegradability, transfection efficiency and cytotoxicity of cationic lipid to overcome the critical barriers of in vitro and in vivo transfection.