Protein-friendly atom transfer radical polymerisation of glycerol(monomethacrylate) in buffer solution for the synthesis of a new class of polymer bioconjugates

A biologically friendly approach is proposed for the synthesis of biocompatible poly(glycerol monomethacrylate) (PGMA) in phosphate-buffer saline, through aqueous Activators ReGenerated by Electron Transfer for Atom Transfer Radical Polymerisation (ARGET ATRP) at ambient temperature, under organic-solvent free conditions which are well tolerated by active proteins. Controlled polymerisation of glycerol monomethacrylate (GMA) was successfully obtained, and this versatile technique was extended to the synthesis of active protein-PGMA conjugates, as PEG alternative for half-life extension of biotherapeutics. Lysozyme was tested as model protein for site-specific grafting-from polymerisations in phosphate buffer. Conjugated PGMA at relatively high degree of polymerisation (DP <= 250) preserved the enzymatic activity of lysozyme (up to 80%) and its stability (80% of retained activity) in serum and in trypsin solution. The combination of aqueous ARGET ATRP techniques and a grafting-from strategy may pave the way for a new generation of nanomedicines based on protein-PGMA conjugates.