Synthesis and Self-Assembly of Well-Defined Elastin-Like Polypeptide–Poly(ethylene glycol) Conjugates

A series of stimulus-responsive elastin-like polypeptide–poly(ethylene glycol) (ELP–PEG) block copolymers was synthesized. The polymeric building blocks were conjugated via the efficient and specific strain-promoted alkyne–azide cycloaddition (SPAAC). For this purpose, ELP and PEG blocks were functionalized with azide and cyclooctyne moieties, respectively. Azides were introduced by applying a recently developed pH-controlled diazotransfer reaction on the primary amines present in ELP (N-terminus and lysine side chains). By varying pH, ELP-blocks with one or two azides were obtained, which subsequently allowed us to synthesize both ELP–PEG diblock copolymers and miktoarm star polymers. Triggering the phase transition of the ELP-block resulted in the formation of an amphiphilic block copolymer, which self-assembled into micelles. This is the first example of an ELP-containing hybrid block copolymer in which PEG as the hydrophilic corona-forming domain is combined with a stimulus-responsive ELP-block. The encapsulation of a hydrophobic fluorescent dye was shown to exemplify the potential of the micelles to serve as nanocarriers for hydrophobic drugs, with the PEG corona providing stealth and steric protection of encapsulated materials.