Thermal- and oxidation dual-responsive random copolymer self-assembly of nanostructures

Abstract

Polymerization-induced self-assembly (PISA) has become a prominent method for creating nanoparticles efficiently. Predominantly, research in this area has centered on block copolymers that often demand a pre-synthesized hydrophilic block paired with a hydrophobic core-forming block. However, we describe an alternative approach, which utilizes a single-step synthesis and PISA of random copolymers composed of hydrophilic N,N-dimethylacrylamide (DMA) and hydrophobic N-acryloyl thiomorpholine (NAT) in an aqueous solution via RAFT polymerization. These manufactured random copolymers self-assemble into nanoparticles of diverse sizes, regulated by the NAT/DMA proportion in the reaction system, without requiring intermediate purification or extra interference. In our study, we reveal that the poly(DMA-co-NAT) random copolymer, with a monomer feed ratio of 7/3, is temperature-sensitive and shows lower critical solution temperature (LCST) behavior. Additionally, NAT pendants have the potential to transform into soluble sulfoxide upon oxidation, which facilitates the alteration and breakdown of the micellar structure in the presence of hydrogen peroxide. Consequently, this one-step system is expanded to the fabrication of nanoscale drug carriers made of polymers. A medicinal drug, doxorubicin, can be effectively encapsulated within the nanostructures during the PISA process and released in a regulated way upon oxidation. Our findings indicate a straightforward, one-step strategy for producing thermal- and oxidation-responsive nanostructures in an aqueous solution via PISA, demonstrating promising potential in the field of drug delivery systems.