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Block Copolymer Crystalline Vesicles with Ultrathin Shell to Extend Blood Circulation Time

Like lipids, amphiphilic block copolymers (BCPs) that are comprised of hydrophobic and hydrophilic segments can self-assemble into various micelle structures depicting curved liquid/liquid interface. Crystallization, which is incommensurate with this curved space, often leads to defect accumulation and renders the structures leaky, undermining their potential biomedical applications. In this talk, I will discuss using an emulsion-solution crystallization method to control the crystallization of an amphiphilic BCP at curved liquid/liquid interface. The resultant BCP crystalsomes (BCCs) structurally mimic classical liposomes yet mechanically are more robust because of the single crystal-like crystalline shell. These BCCs are also nearly impermeable to hydrophilic and hydrophobic drugs. In blood circulation and biodistribution experiments, fluorophore-loaded BCCs show a prolonged circulation half-life. We further demonstrate this excellent performance is attributed to controlled polymer crystallization and the unique BCC nanostructure.