Tunable nano-carriers from clicked glycosaminoglycan block copolymers

Oxime click reaction is used for the synthesis of diblock copolymers of polyethylene glycol (PEG) and glycosaminoglycans (GAGs) with different molecular weights (M_w) and sulfation degrees. The ability of these copolymers to carry positively charged proteins is evidenced by their assembly with poly-l-lysine as a model: interpolyelectrolyte complexes with tunable size at the nanometric scale (radius of 25-90 nm) and narrow distribution are described. We demonstrate that there is a critical M_w of GAGs for the formation of stable complexes and that the sulfation degree determines the size of the nano-assemblies. Highly sulfated GAGs form the smallest complexes that are stable to at least 500 mM ionic strength: a property that is not usual for GAG interpolyelectrolyte complexes. The feasibility of the synthesised block copolymers as protein carriers is further evidenced by their complexation with fibroblast growth factor (FGF-2). The described assets of GAG block copolymers together with the intrinsic GAG properties such as biorecognition and biodegradability open up new opportunities in the design of selective encapsulation/release nanosystems with a stealth PEG corona.