Synthesis, characterization and cellular internalization of poly(2-hydroxyethyl methacrylate) bearing α-D-mannopyranose

2-(alpha-D-Mannopyranosyloxy) ethyl methacrylate (ManEMA) was synthesized in stereochemically pure form, and isolated as an easy-to-handle dry white solid. Poly(ManEMA-co-HEMA)s were prepared by conventional radical copolymerization of ManEMA with 2-hydroxyethyl methacrylate (HEMA). The monomer reactivity ratio r(ManEMA) and r(HEMA) were estimated to be 1.00 and 0.50, respectively. The initial clustering rate of poly(ManEMA-co-HEMA) with a mannose-binding lectin, concanavalin A, evaluated by turbidimetric assay, increased with increasing mole fraction of ManEMA units in the polymer, even at constant ManEMA unit concentration. This cluster glycoside effect of the linear glycopolymer, poly(ManEMA-co-HEMA), could be well interpreted by the sequence distribution of ManEMA units calculated on the basis of the terminal model. The cellular uptake and cytotoxicity of fluorescently labeled poly(ManEMA) was examined in HeLa cells. Confocal laser scanning microscope imaging revealed the endocytotic internalization of poly(ManEMA) in HeLa cells. The survival rate of HeLa cells treated with poly(ManEMA) was estimated to be 95.7 +/- 1.7% versus untreated cells. These results indicate that ManEMA is a promising monomer for development of medicinal glycopolymers.