Cationic Lipids

Introduction

Cationic lipids are amphiphilic small molecules, whose structures analogous to natural phospholipids. The difference is that cationic lipid molecules have a cationic charge on their structure. The amphiphilic of cationic lipids is due to the simultaneous presence of both hydrophobic long hydrocarbon chains and hydrophilic charged group. Cationic lipids as a versatile tool are widely for the delivery of DNA, RNA and many other therapeutic molecules, and are especially attractive because they can be easily designed, synthesized and characterized. Nowadays, an exponentially growing researches has been studied on this topic.

Structure

The structure of cationic lipids is broadly classified into three parts, including positive-charged polar head, linker and hydrophobic tail ^[1].

• A positive-charged polar head exhibits one or more positive charges, the group includes polyamine, quaternary ammonium salt, guanidine, imidazole, etc.
• A linker, with a variable length and nature (often ether, ester, carbamates, amides, disulfide, acylhydrazone, urea, phosphate bond, etc.).
• A hydrophobic tail is largely comprised of alkyl chains of lengths ranging from 12 to 20 carbons or cholesterol and its derivatives.

Fig.1 Representative structure of cationic lipid DOTMA and linker bonds of cationic lipid

Applications

The primary and most important application of cationic lipids is as vectors for the delivery of specific nucleic acids into targeted cells, which provides great convenience for gene therapy of many diseases, even incurable diseases. It can spontaneously self-assemble with anionic nucleic acids to form liposomes through electrostatic interactions, and then protect nucleic acids from nuclease degradation and drive it into cells. Cationic lipids as vectors of gene delivery show great advantages such as simplicity of preparation, good repeatability and biodegradability and potential commercial value. Today, cationic lipids have been proved that can serve as vectors for the delivery of various nucleic acids, including plasmid DNA (pDNA) and messenger RNA (mRNA), as well as short regulatory RNAs.

Fig. 2. Schematic representation of nucleic acids delivery into cells mediated by cationic lipids.

It is worth noting that the each and every constituent domain of cationic lipids, that is, headgroup, linker and hydrophobic tail, all have important role in delivery of nucleic acids ^[2]. The main role of positive-charged polar headgroups is combination with nucleic acid molecules to form liposomes through electrostatic action. And the physical and chemical properties of headgroups, such as size and charge density have a huge impact on the performance of liposomes like stability, thus affecting gene delivery efficiency. The features of the linker, including the overall charge, length and steric hindrance, are responsible for the conformational flexibility of the amphiphile. In other words, the relative orientation of the hydrophobic and cationic moieties affects the interaction of the lipid with nucleic acids, and in turn, the ultimate gene transfer efficiency. Hydrophobic tail plays a role in phase transformation according to structure-activity relationship (SAR) studies, thus affect the mobility, overall stability and cytotoxicity of liposomes composed of cationic lipids and nucleic acids, thus affecting gene delivery efficiency.

Alfa Chemistry can offer all kinds of cationic lipids. You can click on our product list for a detailed view. If you do not find the product you want, we also provide you with custom synthesis service. Please contact us, if you are in need of assistance.

References

1. Zhi D., et al. A review on cationic lipids with different linkers for gene delivery[J]. Advances in Colloid and Interface Science, 2018, 253: 117-140.
2. Ponti F., et al. Cationic lipids for gene delivery: Many players, one goal[J]. Chemistry and Physics of Lipids, 2021, 235: 105032.