Highly Efficient and Versatile Formation of Biocompatible Star Polymers in Pure Water and Their Stimuli-Responsive Self-Assembly

This study demonstrates the rapid and efficient formation of functional core cross-linked star polymers via copper-mediated reversible-deactivation radical polymerization (RDRP) in pure water using fully soluble monomers and cross-linkers. This high throughput arm-first methodology allows the generation of complex nanoarchitectures with tailored core, shell, or periphery- functionalities and is potentially well-suited for biomedical applications given that the macromolecular synthesis is performed entirely in water. To exemplify this approach, different homo- and miktoarm star polymers composed of either poly(N-isopropylacrylamide) (PNIPAM), poly(2-hydroxyethyl acrylate) (PHEA), and poly(ethylene glycol) (PEG) as the polymeric arms are formed. The star products are generated in high yield (8896%) in one-pot and require short reaction times (13 h) and minimal purification steps (dialysis and lyophilization). In addition, the thermal responsivity of PNIPAM-based miktoarm star polymers leading to reversible supramolecular self-assembly is confirmed by DLS and 2D-NOESY NMR analysis. Furthermore, cytotoxicity studies using human embryonic kidney (HEK239T) cells as the model mammalian cells revealed that the star polymers are nontoxic even up to high polymer concentrations (2 mg mL(1)). The simplistic product formation and isolation, combined with the use of water as the polymerization medium, mean that this procedure is highly attractive as a low-cost pathway toward functional, biocompatible organic nanoparticles for commercial applications.