Cationic Lipid

Cat. No. Product Name CAS No.
BPG-3618 Hexadecanedioic Acid Mono-L-carnitine Ester Chloride 42150-38-9 Inquiry
BPG-3619 DOTMA 104162-48-3 Inquiry

Cationic lipids are a class of lipids with positively charged head groups that have been widely studied and exploited due to their ability to form complexes with negatively charged molecules such as nucleic acids, proteins, and other biomolecules. Cationic liposomes are usually composed of a cationic lipid and a neutral auxiliary lipid complexed under appropriate conditions. The transfection efficiency of cationic liposomes is closely related to the composition of the cationic lipids.

The lipid products provided by BOC Sciences include cationic lipids of various specifications and purity, which can meet the different experimental needs of scientific researchers. These products undergo strict quality control and testing to ensure their stability and reliability. In addition, BOC Sciences also provides customized lipid synthesis services, which can synthesize cationic lipids with specific structures and properties according to customers' specific requirements, providing strong support for customers' research projects.

Structure of Cationic Lipids

Cationic lipid molecules are structurally composed of three parts: one or more cationic heads, linker bonds, and hydrophobic tails.

Cationic Heads

The heads of cationic lipids mostly contain amine groups (except lipids containing amidine groups), ranging from simple amino groups to quaternary ammonium salts substituted by methyl or hydroxyethyl groups. The polar heads of cationic lipids play a role in binding liposomes to DNA, and liposome-DNA complexes to cell membranes or other intracellular components. Among cationic cholesterol derivatives, cationic cholesterol compounds with tertiary amine groups have higher transfection activity than quaternary ammonium salt compounds and are much less toxic. The transfection efficiency of cationic liposomes with multivalent polar head groups or multiple positively charged polar heads is higher, which may be because it binds more firmly to DNA and is easier to escape from endosomes.


The length of the linker can affect the interaction between cationic liposomes and cell membranes, thereby affecting transfection viability. Generally speaking, cationic liposomes with long connecting chains can significantly enhance the interaction with cell membranes and achieve high transfection efficiency. Linking bonds are an important component of lipid molecules, which determine the chemical stability and biodegradability of cationic liposomes. The chemical stability of ether bond and C-N bond is high, but it is not easy to be biodegraded and generally not suitable for in vivo experiments. Cationic liposomes containing ester bonds are easily biodegradable and less cytotoxic, but their chemical stability is usually poor. The commonly used connecting bonds are amide bonds and carbamoyl bonds that have high chemical stability but are biodegradable.

Hydrophobic Tails

The hydrophobic tails of common cationic lipids are mainly aliphatic hydrocarbon chains and cholesterol rings. The number of carbon atoms in the aliphatic hydrocarbon chain is usually 12 to 18, so as to provide sufficient fluidity for the lipid bilayer at physiological temperature and maintain a certain rigidity of the lipid bilayer membrane, so as to create conditions for the lipid fusion of cationic liposomes in vivo. For liposomes with fat chain as tail, carbon chain elongation will lead to a decrease in transfection efficiency, but the introduction of unsaturated bonds in the chain can improve the efficiency. The effect of using cholesterol as a hydrophobic tail is often better than that of fat chains, because the bilayer structure formed by it is more stable.

Applications of Cationic Lipids

  • Gene delivery: Cationic lipids are commonly used as carriers to deliver nucleic acids (such as DNA and RNA) into cells for gene therapy, gene editing, and genetic research.
  • Drug delivery: Cationic lipids can encapsulate and deliver therapeutic compounds, including small molecules and biologics, to target tissues or cells to treat various diseases.
  • Vaccine development: Cationic lipids are used to formulate lipid-based nanoparticles for vaccine delivery, enhancing antigen presentation and immunogenicity.
  • Cell membrane modification: Cationic lipids can be used to modify cell membranes, alter membrane permeability, and facilitate uptake of therapeutic agents into cells.

Case Study

Case Study 1

Li et al. developed a chemical library of ionizable cationic lipids via a one-step chemo-bioenzymatic esterification method and further prepared the synthesized ionizable lipids into lipid nanoparticles (LNPs) for mRNA delivery. This method uses a highly efficient biocatalyst commonly used in organic synthesis such as esterification and transesterification: Candida Antarctic lipase B (CALB). Chemo-Biological CALB enzymes can catalyze esterification in one step, and high-throughput development of a series of ionizable cationic lipids for mRNA LNP delivery platforms.

Enzyme-catalyzed one-step synthesis of ionizable cationic lipidsFig. 1. Enzyme-catalyzed one-step synthesis of ionizable cationic lipids (ACS Nano. 2022, 16(11): 18936-18950).

Through the screening of orthogonal design experimental methods, the AA3-DLin LNP with the best performance showed excellent mRNA delivery efficacy and long-term storage capacity. Furthermore, antibody titer, virus challenge, and T-cell immune response studies demonstrated that the AA3-DLin LNP COVID-19 vaccine encapsulating SARS-CoV-2 spike mRNA successfully induced strong immunogenicity in a BALB/c mouse model.

Case Study 2

He et al. used Ugi four-component reaction to multidimensionally design ionizable cationic lipids with organ-targeted mRNA delivery function. Ugi-4CR can synthesize target compounds constructed from four types of reactants: aldehydes, isonitriles, amines and carboxylic acids in a "one-pot" method under mild reaction conditions, avoiding lengthy purification steps of reaction intermediates. The author used the functional groups of the four reactants to provide the ionizable head, connecting structure and hydrophobic tail of ionizable lipid (lL) respectively. Taking advantage of the characteristics of multi-component reactions, a large number of interconnected structural combinations can be obtained with only a small number of reactants involved.

Using multidimensional approach to modulate ionizable lipidsFig. 2. Using multidimensional approach to modulate ionizable lipids (Angewandte Chemie International Edition. 2023, 62(43): e202310401).

The author selected an orthogonal combination of multiple reactants to synthesize a structural library containing a large number of ILs. These ILs were prepared into LNPs and loaded with mRNA encoding firefly luciferase (mFluc), which was evaluated by bioluminescence signal. The authors found that when the reactants were all monofunctional, the resulting IL generally had liver-targeting mRNA delivery properties. However, when the ionizable component is changed to bifunctionality or trifunctionality, the resulting IL has spleen-targeting mRNA delivery properties. And the authors found that in different targeted IL structures, there are obvious patterns in the impact of functional groups from reactants on delivery efficiency. Finally, the authors verified that these two types of organ-targeting ILs have good biosafety, and their organ-targeting properties changed under different administration methods. This work proposes a multi-dimensional design concept from the structural perspective of IL based on Ugi multi-component reaction, providing a new strategy for improving mRNA delivery efficiency and regular organ-targeting design.


  1. Li, Z. et al. Enzyme-Catalyzed One-Step Synthesis of Ionizable Cationic Lipids for Lipid Nanoparticle-Based mRNA COVID-19 Vaccines. ACS Nano. 2022, 16(11): 18936-18950.
  2. He, Z. et al.A Multidimensional Approach to Modulating Ionizable Lipids for High-Performing and Organ-Selective mRNA Delivery. Angewandte Chemie International Edition. 2023, 62(43): e202310401.

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