Enzyme Controlled Transient Phospholipid Vesicles for Regulated Cargo Release

Abstract Metabolism in biological systems involves the continuous formation and breakdown of chemical and structural components, driven by chemical energy. In specific, metabolic processes on cellular membranes result in in situ formation and degradation of the constituent phospholipid molecules, by consuming fuel, to dynamically regulate the properties. Synthetic analogs of such chemically fueled phospholipid vesicles have been challenging. Here we report a bio‐inspired approach for the in situ formation of phospholipids, from water soluble precursors, and their fuel driven self‐assembly into vesicles. We show that the kinetic competition between anabolic and catabolic‐like reactions leads to the formation and enzymatic degradation of the double‐tailed, vesicle‐forming phospholipid. Spectroscopic and microscopic analysis demonstrate the formation of transient vesicles whose lifetime can be easily tuned from minutes to hours. Importantly, our design results in the formation of uniform sized (65 nm) vesicles simply by mixing the precursors, thus avoiding the traditional complex methods. Finally, our sub‐100 nm vesicles are of the right size for application in drug delivery. We have demonstrated that the release kinetics of the incorporated cargo molecules can be dynamically regulated for potential applications in adaptive nanomedicine.