Metabolic glycan labelling with bio-orthogonal targeting and its potential in drug delivery

New modes of targeted drug delivery are emerging with promise of enhancing therapeutic efficacy while reducing side effects. This review examines the landscape of metabolic glycan labelling-a technique gaining traction for its potential in specific drug targeting. By exploiting the natural glycan synthetic pathway of monosaccharides, unnatural sugar analogues are incorporated into glycoproteins, allowing for the presentation of unique functional groups on cells. This enables specific targeting using 'clickable' probes with complementary click chemistry functional groups. The selection of sugar analogues and chemical tags are crucial components explored in this review, alongside considerations for cell lines, tissues, and cargo selection. The review discusses non-therapeutic and therapeutic applications of metabolic glycan labelling, as well as its potential beyond labelling of cell surfaces. The review also highlights underexplored areas of metabolic glycan labelling by assessing the limited literature addressing labelling efficiency, turnover rates, the impact of sugar supplements in cell culture, and the critical cell to functionalised sugar ratio. Furthermore, this review delves into the future landscape and goals of metabolic glycan labelling, envisioning its potential in targeted drug delivery.