Surface mannosylation of dispersion polymerisation derived nanoparticles by copper mediated click chemistry

The synthesis of spherical polymeric nanoparticles containing alkyne surface functionalities for post polymerisation glycosylation is described. The nanoparticles were obtained by a polymerisation induced self-assembly (PISA) inspired methodology in dispersed media by Cu(0) mediated polymerisation. A water soluble poly(ethylene glycol methacrylate-stat-propargyl methacrylate), poly(PEGMA(18)-stat-PgMA(5)), macroinitiator was first synthesised and chain extended with 2-hydroxypropyl methacrylate (HPMA) in water using a copper wire catalyst. It was found that irrespective of the macroinitiator to HPMA ratio and the reaction time the desired spherical morphologies (<100 nm) were obtained while the absence other morphologies suggest a deviation from the classical PISA process due to chain termination in the nanoparticle's core. The obtained nanoparticles contained alkyne functionalities in the shell, which were successfully reacted by copper mediated click chemistry with fluoresceine azide and mannosides with hydrophobic and hydrophilic spacers of different lengths. The obtained mannosylated nanoparticles displayed no significant cytotoxicity against human alveolar basal epithelial adenocarcinomic (A549) cells at any dose <0.5 mg mL(-1). Preliminary binding studies confirm the ability of the mannosylated nanoparticles to bind to human lectin dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN). The methodology reported here is a convenient route to well-defined spherical and shell-functionalisable nanoparticles to create libraries of bio-active nanomaterials.