Shell-Sheddable/Core-Degradable ABA Triblock Copolymer Nanoassemblies: Synthesis via RAFT and Concurrent ATRP/RAFT Polymerization and Drug Delivery Application

Abstract

Exploration of effective approaches that allow for the synthesis of smart block copolymers and their nanoassemblies exhibiting enhanced drug release upon stimuli-responsive degradation is in huge demand for drug delivery and pharmaceutical science. Herein, we report a new approach utilizing a combination of ATRP and RAFT polymerization techniques through sequential RAFT and concurrent ATRP/RAFT polymerization in the presence of an iniferter bearing both disulfide and acetal linkages labeled with terminal bromine (the ATRP initiating moiety) and dithioester groups (the RAFT chain transfer moiety). The approach enables the synthesis of an ABA-type triblock copolymer with both disulfide and acetal linkages at only one block junction as well as disulfide pendants in a hydrophobic block. The flower-type nanoassemblies, formed through aqueous micellization, exhibit dual reduction/ acid responses at core−corona interfaces, leading to the detachment of coronas, as well as reduction response in cores, causing the dissociation of cores. The dual reduction/acid-responsive accelerated and synergistic release profile of an encapsulated doxorubicin, combined with cytotoxicity and cellular uptake in vitro, suggests the great potential of our approach toward effective intracellular drug delivery.

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

“…The acetal and disulfide linkages in the initiator can synergistically accelerate the degradation of the block copolymer at the junction. 75,76 The synthesized TrSP copolymer was then characterized for its amphiphilicity, triple acid/reduction/lightresponsive degradation and controlled release kinetics.…”

Shell‐sheddable and charge switchable magnetic nanoparticle as pH‐sensitive nanocarrier for targeted drug delivery applications

“…18,19 However, reduction of positive charge through PEGylation inhibit the cellular uptake of nanoparticles at the target site. 20 To overcome this PEG dilemma, smart shell-sheddable NPs have been developed that could shed their hydrophilic shells in response to environmental stimuli, such as redox [21][22][23][24] and pH 25 at the extracellular compartment of tumor. 26,27 pH is an attractive trigger for shedding of shell at tumor tissue, since the pH values in tumors are lower than in normal tissues (pH = 7.4).…”