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We report on the preparation of reduction-responsive amphiphilic block copolymers containing pendent p-nitrobenzyl carbamate (pNBC)-caged primary amine moieties by reversible addition-fragmentation chain transfer (RAFT) radical polymerization using a poly(ethylene glycol)-based macro-RAFT agent. The block copolymers self-assembled to form micelles or vesicles in water, depending on the length of hydrophobic block. Triggered by a chemical reductant, sodium dithionite, the pNBC moieties decomposed through a cascade 1,6-elimination and decarboxylation reactions to liberate primary amine groups of the linkages, resulting in the disruption of the assemblies. The reduction sensitivity of assemblies was affected by the length of hydrophobic block and the structure of amino acid-derived linkers. Using hydrophobic dye Nile red (NR) as a model drug, the polymeric assemblies were used as nanocarriers to evaluate the potential for drug delivery. The NR-loaded nanoparticles demonstrated a reduction-triggered release profile. Moreover, the liberation of amine groups converted the reduction-responsive polymer into a pH-sensitive polymer with which an accelerated release of NR was observed by simultaneous application of reduction and pH triggers. It is expected that these reduction-responsive block copolymers can offer a new platform for intracellular drug delivery.

An adenosine triphosphate (ATP)-fueled micellar system in the out-of-equilibrium state was constructed based on 4,5-diamino-1,3,5-triazine (DAT)-containing block copolymer. The block copolymer self-assembled into spherical micelles in equilibrium steady state at pH higher than its p K. The pendant DAT residues in protonated form acted as ATP catchers via hydrogen bonding and electrostatic interactions. Activated by ATP fuel, the polymeric micelles spontaneously disrupted into small aggregates of ATP/polymer hybrid complexes. The consumption of ATP energy via the enzymatic hydrolysis led to dissociation of the complexes and reversible formation of polymeric micelles. A transient self-assembly cycle, in which the assembly underwent autonomous division-fusion motion, was created using ATP fuel and enzyme; the switching of assembly structure was sustained by continuous supply of ATP fuel. This DAT-containing block copolymer have good biocompatibility, and drug-loaded micelles display ATP-responsive release behavior. It is expected that this ATP-fueled supramolecular assembly system will provide a functional platform for biomimic chemistry and therapeutic applications.