Adamantane‐Terminated Polypeptides: Synthesis by N‐Carboxyanhydride Polymerization and Template‐Based Self‐Assembly of Responsive Nanocontainers via Host–Guest Complexation with β‐Cyclodextrin

The synthesis of adamantane‐terminated polypeptides by N‐carboxyanhydride (NCA) polymerization and their use in the template‐based self‐assembly of redox‐responsive nanocontainers is described. Cyclodextrin vesicles (CDV) serve as a supramolecular template to anchor adamantane terminated polypeptides on to the surface of CDV and to form polypeptide shelled vesicles (PPSVss) which are stabilized by crosslinking with cystamin. Polypeptides are characterized by nuclear magnetic resonance, matrix‐assisted laser desorption/ionization (MALDI), and gel permeation chromatography, and nanocontainer formation at each step is confirmed by dynamic light scattering (DLS) and zeta potential measurements. MALDI confirms the presence of the adamantane at the end of the polymers, and isothermal titration calomatry (ITC) of the adamantane‐terminated polypeptides with β‐cyclodextrin proves the capability of adamantane on the polypeptides to form host–guest inclusion complexes even with the longest polypeptides. Encapsulation of a model dye carboxyfluorescein in PPSVss and its redox‐responsive release demonstrates the potential use of this novel type of completely biodegradable and biocompatible nanocontainer for the purpose of intracellullar delivery. The combination of end‐functionalized polypeptides made by ring opening polymerization of N‐carboxyanhydrides, self‐assembly of polypeptide nanocontainers on a supramolecular template, and redox‐responsive contents release, provides opportunities for the design of fully biodegradable nanocarriers for intracellular delivery.