Stepwise Drug-Release Behavior of Onion-Like Vesicles Generated from Emulsification-Induced Assembly of Semicrystalline Polymer Amphiphiles

Tailoring unique nanostructures of biocompatible and degradable polymers and the consequent elucidation of shape effects in drug delivery open tremendous opportunities not only to broaden their biomedical applications but also to identify new directions for the design of nanomedicine. Cellular organelles provide the basic structural and functional motif for the development of novel artificial nanoplatforms. Herein, aqueous onion-like vesicles structurally mimicking multicompartmentalized cellular organelles by exhibiting exquisite control over the molecular assembly of poly(ethylene oxide)-block-poly(epsilon-caprolactone) (PEO-b-PCL) semicrystalline amphiphiles are reported. Compared to in situ self-assembly, emulsification-induced assembly endows the resulting nanoaggregates of PEO-b-PCL with structural diversity such as helical ribbons and onion-like vesicles through the molecular packing modification in the hydrophobic core with a reduction of inherent crystalline character of PCL. In particular, onion-like vesicles composed of alternating walls and water channels are interpreted by nanometer-scale 3D visualization via cryogenic-electron tomography (cryo-ET). Interestingly, the nature of the multi-walled vesicles results in high drug-loading capacity and stepwise drug release through hydrolytic cleavage of the PCL block. The crystalline arrangement of PCL at the molecular scale and the spatial organization of assembled structure at the nanoscale significantly affect the drug-release behavior of PEO-b-PCL nanovehicles.