Hybrid Poly(ß‐Amino Ester) Triblock Copolymers Utilising A Raft Polymerisation Grafting‐From Methodology.

Abstract The biocompatibility, biodegradability and responsiveness of poly(ß‐amino esters) (PBAEs) has led to their widespread use as biomaterials for drug and gene delivery. Nonetheless the step growth polymerisation mechanism which yields PBAEs limits the scope for their structural optimisation towards specific applications because of limited monomer choice and end‐group modifications. Moreover, to date the post‐synthetic functionalisation of PBAEs has relied on grafting‐to approaches, challenged by the need for efficient polymer‐polymer coupling and potentially difficult post conjugation purification. Here a novel grafting‐from approach to grow reversible addition‐fragmentation chain transfer (RAFT) polymers from a PBAE scaffold is described. This was achieved through PBAE conversion into a macromolecular chain transfer agent through a multi‐step capping procedure, followed by RAFT polymerisation with a range of monomers to produce PBAE‐RAFT hybrid triblock copolymers. Following successful synthesis, the potential biological applications of these ABA triblock copolymers were illustrated through assembly into polymeric micelles and encapsulation of a model hydrophobic drug, followed by successful nanoparticle (NP) uptake in breast cancer cells. The findings demonstrate this novel synthetic methodology can expand the scope of PBAEs as biomaterials. This article is protected by copyright. All rights reserved