Small Molecule Liposome Conjugation

Small Molecule Liposome Conjugation

Some functional small molecules can be modified on the surface of liposomes to improve the properties of liposomes. As a leading CRO, BOC Sciences is capable of providing small molecule liposome conjugation service to propose innovative solutions in the field of drug delivery.


Liposomes are self-assembled spherical vesicles containing phospholipid bilayers and hydrophobic cavities, which are non-toxic, biodegradable, and non-allergenic, and can be used to encapsulate and transport a variety of drugs, nutrients, and functional factors, thus improving the stability and bioavailability of these bioactive substances. However, conventional liposomes still have disadvantages such as poor stability, poor active targeting, and insufficient in vivo circulation time. To remedy the shortcomings of conventional liposomes, some biologically active small molecules can be modified on the surface of liposomes by forming bioadhesive and polymeric layers through coupling to improve drug delivery. Such small molecules include vitamins, saccharides, glycosides and sapogenins, etc.

Coupling Methods

There are two main ways of coupling small molecules to liposomes, they are covalent and non-covalent coupling. Covalent coupling is more commonly used, i.e., hydrophobic groups on liposomes are covalently bound to small molecule ligands, commonly used hydrophobic group donors are long-chain fatty acids (e.g., palmitic acid) and phospholipids (e.g., phosphatidylethanolamine (PE) and phosphatidylcellulose (PI)). Covalent coupling of ligands to liposomes normally refers reacting the targeted small molecules with the coupling agent and then with the liposome to form a small molecules-modified liposome.


Folic acid as a small molecule targeting material has the advantages of high stability, high penetration ability, high affinity to the receptor, weak immunogenicity and low cost. The interaction between a folic acid-targeted agent and its tumor surface folic acid receptor can be achieved by a specific endocytosis process. For example, folate liposomes were prepared by linking folic acid with polyethylene glycol diamine as carriers of Doxorubicin to significantly improve target recognition to tumor cells.

Desialic acid glycoprotein receptors are specifically present on the surface of mammalian cells and specifically recognize oligosaccharide proteins with galactose residues or acetylamino galactose residues. Liposomes modified by covalent coupling using galactose derivatives have significantly increased efficiency of hepatic targeting and low drug toxicity, facilitating wide clinical application. Glucose active transport carriers distributed on the brush border side of intestinal mucosal epithelial cells have a strong affinity for glucose. The use of glucose to modify the liposome surface can enhance the affinity of the receptor ligand to facilitate trans-intestinal absorption of the target carrier drug.

Galectin has a specific affinity for β-galactoside and specifically recognizes, galactose, lactose, etc, playing an important role in many physiological and pathological processes such as cell adhesion, apoptosis, inflammatory response, and tumor metastasis. Recently, liposome conjugated with small molecule drug based on galectin receptor-mediated specific glycosyl modifications have been widely applied to tumor targeted therapy.

Soybean glycoside, an extracted component of soybean oil, and its modified liposomes can also achieve hepatic parenchymal cell targeting. For example, the addition of soy glycosides to cationic liposomes can significantly improve the encapsulation rate and cell transfection rate of liposomes.

Liposomes modified with cyclic compounds such as macrocyclic polyamines and benzothiazoles have better properties such as high transfection rate and low cytotoxicity. By modifying the hydrophilic head of liposomes with benzothiazole, the liposome shows more higher transfection efficiency under serum conditions.

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