One-Pot Synthesis of an Amphiphilic ABC Triblock Copolymer PEO-b-PEHOx-b-PEtOz and Its Self-Assembly into Nanoscopic Asymmetric Polymersomes

We report an efficient one-pot synthesis of a new biocompatible amphiphilic ABC triblock terpolymer: poly(ethylene oxide)- block -poly(2-(3-ethylheptyl)-2-oxazoline)- block -poly(2-ethyl-2-oxazoline) (PEO- b -PEHOx- b -PEtOz) using sequential microwave-assisted polymerization. Depending on the hydrophilic weight fraction of the terpolymers, nanoscopic micelles, worms, and polymersomes, as well as multicompartment vesicles, were formed. The self-assemblies were thoroughly analyzed regarding their size and shape using dynamic and static light scattering, TEM, and cryogenic TEM. By varying the ratio of PEO to PEtOz, we were able to drive the asymmetry of the polymersome membranes, which was proved by two independent methods, bicinchoninic acid assay and 2D- 1 H-NOESY NMR spectroscopy, which confirmed the presence of a longer PEO block (45 units) and the absence of a shorter PEtOz (less than 32 units) on the outer surface of the polymersomes. Thus, from this new family of ABC triblock terpolymers, asymmetric polymersomes with a thin membrane (6-10 nm) can be obtained, justifying the potential use in biomedical applications with the direct insertion of transmembrane proteins.