Nonequilibrium Reshaping of Polymersomes via Polymer Addition.

Polymersomes are a class of artificial liposomes, assembled from amphiphilic synthetic block copolymers, holding great promise toward applications in nanomedicine. The diversity in polymersome morphological shapes and, in particular, the precise control of these shapes, which is an important aspect in drug delivery studies, remains a great challenge. This is due to a lack of general methodologies that can be applied and the inability to capture the morphologies at the nanometer scale. Here, we present a methodology that can accurately control the shape of polymersomes via the addition of polyethylene glycol (PEG) under nonequilibrium conditions. Various shapes including spheres, ellipsoids, tubes, discs, stomatocytes, nests, stomatocyte-in-stomatocytes, disc-in-discs, and large compound vesicles (LCVs) can be uniformly captured by adjusting the water content and the PEG concentration. Moreover, these shapes undergo nonequilibrium changes in time, which is reflected in their phase diagram changes. This research provides a universal tool to fabricate all shapes of polymersomes by controlling three variables: water content, PEG concentration, and time. The use of the biofriendly polymer PEG enables the application of this methodology in the field of nanomedicine.

Dynamic Loading and Unloading of Proteins in Polymeric Stomatocytes: Formation of an Enzyme-Loaded Supramolecular Nanomotor.

Self-powered artificial nanomotors are currently attracting increased interest as mimics of biological motors but also as potential components of nanomachinery, robotics, and sensing devices. We have recently described the controlled shape transformation of polymersomes into bowl-shaped stomatocytes and the assembly of platinum-driven nanomotors. However, the platinum encapsulation inside the structures was low; only 50% of the structures contained the catalyst and required both high fuel concentrations for the propelling of the nanomotors and harsh conditions for the shape transformation. Application of the nanomotors in a biological setting requires the nanomotors to be efficiently propelled by a naturally available energy source and at biological relevant concentrations. Here we report a strategy for enzyme entrapment and nanomotor assembly via controlled and reversible folding of polymersomes into stomatocytes under mild conditions, allowing the encapsulation of the proteins inside the stomach with almost 100% efficiency and retention of activity. The resulting enzyme-driven nanomotors are capable of propelling these structures at low fuel concentrations (hydrogen peroxide or glucose) via a one-enzyme or two-enzyme system. The confinement of the enzymes inside the stomach does not hinder their activity and in fact facilitates the transfer of the substrates, while protecting them from the deactivating influences of the media. This is particularly important for future applications of nanomotors in biological settings especially for systems where fast autonomous movement occurs at physiological concentrations of fuel.