Synthesis and Dual-Acid/Light-Responsive Disassembly of Amphiphilic Block Copolymer Nanoassemblies Bearing Conjugated Benzoic Imine Pendants

Stimuli-responsive degradable amphiphilic block copolymers(SRD-ABPs)have been extensively explored as a promising building block in theconstruction of smart nanoassemblies exhibiting controlled/enhancedrelease of encapsulated molecules including therapeutics. Recent advanceinvolves the development of effective approaches to synthesize dualSRD-ABPs and their nanoassemblies, most of which are conventionallydesigned with two different cleavable linkages (different functionalgroups), thus responding to two stimuli, typically acid-labile andphotoresponsive groups. Herein, we report a new approach to achievedual acidic pH/light responses with a single labile linkage employingconjugated benzoic imine chemistry. As a proof-of-concept investigationof the approach, a well-defined poly-(ethylene glycol)-based SRD-ABPcontaining conjugated benzoic imine pendants in the hydrophobic blockwas synthesized by a combination of reversible deactivation radicalpolymerization and postpolymerization modification. The synthesizedcopolymer self-assembled in an aqueous solution to form colloidallystable nanoassemblies, consisting of acid/light-degradable hydrophobiccore bearing conjugated imine linkages surrounded with hydrophiliccoronas. Upon dual responses to acidic pH and UV/visible light, thenanoassemblies degraded through a change in the hydrophobic/hydrophilicbalance of micelle cores. This work demonstrates the versatility ofa new approach to design and develop advanced nanoassemblies exhibitingdual-acid/light responses on a single conjugated benzoic imine group,thus being effective for intracellular drug delivery.