Shell-Sheddable/Core-Degradable ABA Triblock CopolymerNanoassemblies: Synthesis via RAFT and Concurrent ATRP/RAFTPolymerization and Drug Delivery Application br

Exploration of effective approaches that allow for thesynthesis of smart block copolymers and their nanoassemblies exhibitingenhanced drug release upon stimuli-responsive degradation is in hugedemand for drug delivery and pharmaceutical science. Herein, we report anew approach utilizing a combination of ATRP and RAFT polymerizationtechniques through sequential RAFT and concurrent ATRP/RAFTpolymerization in the presence of an iniferter bearing both disulfide andacetal linkages labeled with terminal bromine (the ATRP initiatingmoiety) and dithioester groups (the RAFT chain transfer moiety). Theapproach enables the synthesis of an ABA-type triblock copolymer withboth disulfide and acetal linkages at only one block junction as well asdisulfide pendants in a hydrophobic block. Theflower-type nano-assemblies, formed through aqueous micellization, exhibit dual reduction/acid responses at core-corona interfaces, leading to the detachment ofcoronas, as well as reduction response in cores, causing the dissociation of cores. The dual reduction/acid-responsive accelerated andsynergistic release profile of an encapsulated doxorubicin, combined with cytotoxicity and cellular uptakein vitro, suggests the greatpotential of our approach toward effective intracellular drug delivery.