Flower-like Micelles of Polyethylene Oxide End-Capped with Cholesterol

Nanostructures self-assembled from natural or biocompatible macromolecules attract increasing attention due to their potential in nanomedical and technological applications. Self-assembly and structural properties of flower-like micelles formed by cholesterol end-capped polyethylene oxide (PEO) have been investigated by contrast-variation small-angle neutron scattering, small-angle X-ray scattering, dynamic light scattering, and molecular dynamics (MD) simulations. Three molecular weights (MWs) of the middle PEO block, (6, 10, and 20 kg/mole) have been synthesized and examined individually. As expected, the critical micelle concentration increases with PEO block length and for the two higher MW polymer samples, flower-like micelles coexist with unimers. A core–two-shell model was applied to analyze the small-angle neutron and X-ray scattering data, showing that in all cases, the cholesterol core of micelles is about 24 Å in radius and practically free of water, while the PEO corona contains a denser inner shell with about 50% of water and a well-hydrated outer shell (>88%). MD simulations with the same number of cholesterol units in the core based on the experimental outcome revealed a somewhat ellipsoidal cholesterol core with an average radius ∼24 Å, inner PEO shell, and well-hydrated outer shell, consistent with the experimental analysis. For all micelles studied, the PEO block was found to be slightly extended (∼30%) compared to the free coil configuration, while the cholesterol core and inner PEO shell were found to be very similar implying comparable aggregation numbers, nearly independent of the PEO length. The polymer concentration was below the overlap limit, and we observe well-defined stable non-clustering flower-like micelles, which have a nice potential for biomedical applications. This study provides a universal approach to unambiguously identify the morphology of flower-like micelles with detailed internal structural and compositional information.