Microwave Irradiation-Assisted Reversible Addition–Fragmentation Chain Transfer Polymerization-Induced Self-Assembly of pH-Responsive Diblock Copolymer Nanoparticles

[Image: see text] Herein, we present a versatile platform for the synthesis of pH-responsive poly([N-(2-hydroxypropyl)]methacrylamide)-b-poly[2-(diisopropylamino)ethyl methacrylate] diblock copolymer (PHPMA-b-PDPA) nanoparticles (NPs) obtained via microwave-assisted reversible addition–fragmentation chain transfer polymerization-induced self-assembly (MWI-PISA). The N-(2-hydroxypropyl) methacrylamide (HPMA) monomer was first polymerized to obtain a macrochain transfer agent with polymerization degrees (DPs) of 23 and 51. Subsequently, using mCTA and 2-(diisopropylamino)ethyl methacrylate (DPA) as monomers, we successfully conducted MWI-PISA emulsion polymerization in aqueous solution with a solid content of 10 wt %. The NPs were obtained with high monomer conversion and polymerization rates. The resulting diblock copolymer NPs were analyzed by dynamic light scattering (DLS) and cryogenic-transmission electron microscopy (cryo-TEM). cryo-TEM studies reveal the presence of only NPs with spherical morphology such as micelles and polymer vesicles known as polymersomes. Under the selected conditions, we were able to fine-tune the morphology from micelles to polymersomes, which may attract considerable attention in the drug-delivery field. The capability for drug encapsulation using the obtained in situ pH-responsive NPs, the polymersomes based on PHPMA(23)-b-PDPA(100), and the micelles based on PHPMA(51)-b-PDPA(100) was demonstrated using the hydrophobic agent and fluorescent dye as Nile red (NR). In addition, the NP disassembly in slightly acidic environments enables fast NR release.