Synthesis of multiple stimuli-responsive degradable block copolymers via facile carbonyl imidazole-induced postpolymerization modification

Abstract

Smart block copolymers that exhibit degradability or reversibility in response to multiple stimuli or environments (MSRD-exhibiting block copolymers) have been explored as effective building blocks in materials and pharmaceutical sciences. Despite the increasing demand to develop multiple stimuli-responsive degradable block copolymers, their synthesis via both direct polymerization of degradable monomers and postpolymerization modification is challenging. Herein, we report a robust approach to synthesize a triple stimuli-responsive degradable block copolymer labeled with two acid-cleavable acetal and one reduction-cleavable disulfide linkages on the backbone and pendant light-cleavable o-nitrobenzyl groups in the hydrophobic block. The strategy centers on carbonyl imidazole chemistry to explore atom transfer radical polymerization of carbonyl imidazole methacrylate in the presence of a dual acid/reduction-responsive degradable bifunctional initiator, followed by carbonyl imidazole-induced postpolymerization modification with an o-nitrobenzyl amine. A well-defined ABA-type block copolymer and its self-assembled nanoassemblies respond to triple stimuli acid/reduction/light and thus exhibit on-demand sustained or rapid model drug release depending on the type of stimulus presented. We envisage that the present study offers new technique to the postpolymerization modification toolbox with outstanding adaptability to ATRP, which can be utilized for synthesizing various single and MSRD block copolymers.