Conformation-Directed Micelle-to-Vesicle Transition of Cholesterol-Decorated Polypeptide Triggered by Oxidation

Abstract

Hierarchical self-assembly of synthetic polypeptides has attracted increasing interests due to its protein-mimetic structure and great potential in nanotechnology and biomedical applications. However, controlling the morphology and function of polymeric nanostructures via secondary structures remains largely unexplored. Here, we report an unusual micelle-to-vesicle transformation of cholesterol-decorated poly(l-cysteine) copolymer assemblies in response to reactive oxygen species (ROS). We found that the interesting morphological transition correlates with the alteration in conformations from β-sheet to α-helix, which grants an attractive "on-off" switch for triggered release and cellular interaction. We further demonstrated the usefulness of the conformation-regulated assembly strategy both in vitro and in vivo, taking cancer treatment as a model. The work offers a new insight on the folding and hierarchical assembly of polypeptides and a novel approach for the development of smart platforms in biosensing, disease treatment, and diagnostic applications.