engleski

Functional glyconanomaterials based on bacterial peptidoglycan for targeted drug delivery and surface recognition studies

Molecular nanotechnology includes different and powerful new tools for understanding biological processes and the treatment of human diseases. Liposomes are biodegradable and non-toxic assemblies that are recognized as valuable drug delivery systems as well as artificial biological membranes. Peptidoglycan (PGN) is the major component of bacterial cell walls which is recognized by the innate immune system through a series of pattern recognition receptors (PRR), which play a key role in the first-line defense of the body. Lectins, naturally occurring carbohydrate-binding proteins, are involved in numerous biological processes and some of them act as PRR and bind significantly to PGN. Therefore, extensive studies are carried out on the development of functional nanosystems for PRR targeting in the fields of infectious diseases and cancer research. In our study, we were primarily interested in the design and preparation of glycosylated liposomes whose surfaces are decorated with peptidoglycan monomer, the disaccharide pentapeptide β-D-GlcNAc-(1→ 4)-D-MurNAc-L-Ala-D-isoGlu-mesoA2pm-(εNH2)-D-Ala- D-Ala, (PGM). PGM is a repeating unit of B. divaricatum cell wall PGN. To incorporate the PGM into the lipid bilayer, lipophilic derivative, PGM-oleyl was synthesized. PGM-modified liposomes with various amounts of entrapped PGM-oleyl were prepared and characterized. It was shown that incorporation of PGM-oleyl into liposomes affects the size and surface charge of liposomes, the size and zeta potential were decreased in regard to PC liposomes. The presence of PGM, i.e., GlcNAc on the surface of the liposomes was confirmed by measuring an increase of the mean liposome size in suspensions after the addition of model lectin, wheat germ agglutinin (WGA), specific for terminal N-acetylneuraminic acid and GlcNAc units. It was demonstrated that PGM was effectively recognized by WGA. Since peptidoglycan recognition by PRRs involves moderate to high-affinity interactions with the carbohydrate moiety as well as the peptide moiety of peptidoglycan, the established platform could be successfully employed in targeted drug delivery and analyses of lectin-carbohydrate interactions.

gylconanomaterials

nije evidentirano