Recent advances in liposome technology have focused on bioconjugation strategies to improve drug loading, targeting and overall efficacy. As a novel targeting molecule (or ligand), aptamer is widely used in the modification of nanocarriers such as liposomes, and has received increasing attention from pharmaceutical researchers because it can specifically bind to tumor markers on the surface of tumor cells, thus aptamer-liposome bioconjugates can greatly improve the targeting efficiency of drug-loaded liposomes to tumor cells, achieve precise drug delivery and increase efficacy and reduce toxicity.
As a leading CRO, BOC Sciences is committed to providing custom bioconjugation services. We have the ability to conjugate aptamers to liposomes to provide innovative solutions for drug delivery.
Aptamers are a class of single-stranded oligonucleotides with high specificity, strong affinity, and precise target recognition, including RNA and single-stranded DNA. Aptamers can form a specific three-dimensional spatial configuration by folding secondary and tertiary structures, and then bind to different target molecules with high specificity and affinity by van der Waals forces, hydrogen bonding, electrostatic interactions, base stacking forces, etc. Aptamers with high specificity and strong affinity for the target can be obtained after in vitro amplification and multiple iterations of screening. Aptamers are characterized by wide range of target molecules, high stability, non-immunogenicity, easy penetration into tissues, low price, easy synthesis and modification, etc. They have broad application prospects in biomarker discovery, cancer diagnosis and targeted drug delivery system development.
Liposomal drug carriers, one of the most common formulations for reducing drug toxicity and improving targeting, consist of lipid bilayer vesicles formed by dispersing phospholipids and cholesterol in water. The polar groups are in contact with water, and the non-polar groups are joined to each other to form a bilayer, so that the inside of the bilayer and the vesicles can encapsulate fat-soluble drugs and water-soluble drugs, respectively, thus playing the role of drug carriers. By coupling with aptamers, the targeting specificity of liposomes is significantly enhanced.
Aptamers can be attached to liposomes using covalent bonding (preconjugation to lipids) or post-insertion methods.
Covalent bonding techniques commonly employ 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) chemistry and thiol-maleimide linkage reactions. For example, an aptamer with a sulfhydryl functional group is incubated with a liposome having a maleimide-activated PEG-DOPE surface structure, and after washing and purification, a bioconjugation of the target aptamer with the liposome can be prepared.
The post-insertion method reacts functional group-activated lipids to aptamers to create unstable micelles, which are then mixed with preformed liposomes to incorporate the aptamer-lipids into the liposome membrane.
The development of antitumor drug delivery systems is the most promising and important application area for aptamer-liposome conjugates. Recent years, aptamers screened with some clinically important tumor markers or biomarkers as targets have gained rapid development in tumor targeting research. For example, nucleolin ( NCL, C23 ) is highly expressed in breast cancer cell membranes and its specific aptamer AS1411 is often used for breast cancer targeting liposome studies. The aptamer AS1411 modified liposome conjugates can enhance the killing effect on breast cancer cells and improve the antitumor effect on breast cancer xenografts when compared with normal liposomes. The corresponding aptamer GT75, a novel aptamer of eEF1A containing 75 GT repeats, has great potential for both targeting and therapeutic functions in hepatocellular carcinoma. Cancer-targeting liposomes has been developed by attaching anti-EGFR aptamers carrying quantum dots and therapeutic siRNAs to the surface of liposomes for therapeutic strategies.