Glycopolymer-grafted nanoparticles as glycosaminoglycan mimics with cell proliferation and anti-tumor metastasis activities

Glycosaminoglycans (GAGs) are naturally existing extracellular components with a variety important biological functions. However, their heterogeneous chemical compositions and the challenges in purification have become the main disadvantages for clinical applications. Thus, various synthetic glycopolymers have been designed to mimic the structures and functions of natural GAGs. In the current study, glycopolymers from structurally simple glucose or N-acetylglucosamine monomers were synthesized, which were further subjected to sulfation of different degrees and grafting onto silica nanoparticles, leading to spherical-shaped nano-structures of uniform diameters. With the successively strengthened multivalent effect, the obtained glycopolymer nanoparticles not only showed excellent effects on promotion of cell proliferation by stabilizing growth factors, but also significantly inhibited tumor metastasis by weakening the adhesion between tumor cells and activated platelets. Among the prepared nanoparticles, S3-PGNAc@Si with N-acetylglucosamine segment and the highest sulfation degree exhibited the strongest bioactivities, which were even close to those of heparin. This work presents a novel approach for structural and functional mimicking of natural GAGs from simple and low-cost monosaccharides, holding great potential for a range of biomedical applications.