Facile Strategies to Synthesize Dual Location Dual Acidic pH/Reduction-Responsive Degradable Block Copolymers Bearing Acetal/Disulfide Block Junctions and Disulfide Pendants

[Image: see text] We report new dual acidic pH/reduction-responsive degradable amphiphilic block copolymers featured with dual acidic pH-labile acetal linkage and a reductively-cleavable disulfide bond at the hydrophilic/hydrophobic block junction as well as pendant disulfide bonds in the hydrophobic block. Centered on the use of a macroinitiator approach, three strategies utilize the combination of atom transfer radical polymerization and reversible addition fragmentation chain transfer polymerization in a sequential or concurrent mechanism, along with facile coupling reactions. Combined structural analysis with dual-stimuli-responsive degradation investigation allows better understanding of the architectures and orthogonalities of the formed block copolymers as a diblock or a triblock copolymer. Our study presents the development of effective synthetic strategies to well-defined multifunctional amphiphilic block copolymers that exhibit dual-stimuli-responsive degradation at dual location (called the DL-DSRD strategy), thus potentially promising as nanoassemblies for effective drug delivery.