One‐Pot/Simultaneous Synthesis of PHPMA‐G‐PLA Copolymers via Metal‐Free Rop/Raft Polymerization and their Self‐Assembly from Micelles to Thermoresponsive Vesicles.

The present article reports a simple and straightforward approach to access thermoresponsive graft copolymers based on lactide (LA) and a methacrylic monomer, 2‐hydroxypropyl methacrylate (HPMA), using a synthesized carboxy‐functionalized trithiocarbonate‐based chain transfer agent. One protocol involves a metal‐free simultaneous synthesis through a combination of reversible addition‐fragmentation chain transfer polymerization and organic acid‐catalyzed ring‐opening polymerization, which follows first‐order kinetics. The resulting copolymers with a controlled structure exhibit remarkably narrow molecular weight distributions (Ð < 1.10). Within this framework, the self‐assembly of PHPMA‐g‐PLA graft copolymers (GCs) into nanoparticles (NPs) is demonstrated at concentrations of 0.2 and 0.5 wt.%, respectively. The displacement method, based on the rapid injection of the organic solvent (acetone) into an aqueous medium under vigorous stirring, produces spherical NPs such as micelles, vesicles, or non‐spherical "lumpy rods". The presence of a pseudo‐thermoresponsive segment (PHPMA) in GCs facilitates stimulus‐responsive self‐assembly behavior. Well‐defined spherical NPs—primarily vesicles of substantial size—develop upon heating above the glass transition temperature (Tg ≈35–36 °C) of the GCs in an acetone–water (80/20 wt.%) mixture. Last, specific interactions between the obtained PHPMA‐g‐PLA nano‐objects and blood proteins in human plasma are studied using isothermal calorimetry. [ABSTRACT FROM AUTHOR]