Multifunctionalized Brush-Like Glycopolymers with High Affinity to P-Selectin and Antitumor Metastasis Activity.

Abstract

Glycopolymers that can mimic natural glycosaminoglycan, such as heparin, have shown great potentials in inhibition of cancer metastasis. In the current work, a novel series of brush-like glycopolymers (BGPs) with simultaneous functionalization of various monosaccharide or disaccharide compositions have been synthesized through a new grafting-polymerization strategy, in order to mimic the activities of both heparin and P-selectin ligand PSGL-1. In the subsequent in vitro assays of antiadhesion, platelets activation, heparanase inhibition, and so on, BGP-SFH, as one of the BGPs with the composition of the combined three sugar units, sialic acids, fucoses, and heparin disaccharides, showed the highest antimetastasis ability, similar to its prototype heparin. Moreover, in a mouse metastatic melanoma model, the BGP-SFH also inhibited B16 cell metastasis effectively. Thus, the current work not only demonstrated a type of promising antimetastasis glycopolymer BGPs, but also illustrated an easy synthetic approach to multifunctionalized glycopolymers, leading to potential applications for broader biomedical research.