Solid-Phase Glycolipid Synthesis Expedites Liposome Functionalization

Glycolipids play important roles in immune modulation, which makes them attractive components for vaccine delivery systems. However, access to these molecules remains a major limitation as most synthetic approaches rely on arduous solution-phase strategies. Here, we report a unified solid-phase platform that combines automated glycan assembly and iterative amide couplings for the rapid on-resin generation of a variety of mannan- and Gb3-derived glycolipids. This modular method enables the systematic diversification of glycan and lipid-anchor domains within a single synthetic framework. The synthetic constructs were used to generate glyco-functionalized liposomal nanoparticles with potential for immune cell targeting. Preliminary biological studies demonstrate efficient cell-associated uptake by antigen-presenting cells and show that biological performance is governed not only by glycan identity but also by anchor architecture.