Cell-Selective Metabolic Glycan Labeling Based on Ligand-Targeted Liposomes

Abstract

A cell-specific metabolic glycan labeling strategy has been developed using azidosugars encapsulated in ligand-targeted liposomes. The ligands are designed to bind specific cell-surface receptors that are only expressed or up-regulated in target cells, which mediates the intracellular delivery of azidosugars. The delivered azidosugars are metabolically incorporated into cell-surface glycans, which are then imaged via a bioorthogonal reaction.

Dynamic Sialylation in Transforming Growth Factor-β (TGF-β)-induced Epithelial to Mesenchymal Transition

“…The immunoblot analysis of azide-labled sialylated glycoproteins was performed as described previously (24). For other immunoblot detections, the blocked membrane was incubated for 1 h at 4°C with a primary antibody (1:1,000 to 1:3,000 dilution) in blocking buffer.…”

Glycocalyx Remodeling with Proteoglycan Mimetics Promotes Neural Specification in Embryonic Stem Cells

“…This can be achieved through manipulation of metabolic pathways responsible for glycan biosynthesis, 7 by covalent grafting of glycans to surface proteins, 8 or through passive insertion of lipid-functionalized glycoconjugates into the cell membrane. 9 The latter approach is particularly appealing, as it has minimal impact on existing membrane structures.…”

Realizing the promise of chemical glycobiology

“…However, a potential limitation of the metabolic glycan imaging is the lack of cell type or tissue specificity, as the injected sugar precursors would be incorporated into all the shared glycan biosynthetic pathways. A recently reported cell-specific metabolic labeling strategy that uses ligand-targeted liposomes to encapsulate and selectively deliver azidosugar precursor to target cells provides a promising solution to this circumvent this problem [115]. Future studies should be directed to the exploration of novel biosynthetic pathways to cover additional types of glycans in the glycome, and to understanding their limitations, when sugar precursors are biosynthetically used for more than one purpose [116]; new unnatural sugar precursors can be envisaged that possess better biocompatibility and favorable pharmacokinetic properties; and new orthogonal chemical reporters are needed that permit simultaneous imaging of different types of glycans in real time.…”