Copolymer Self-Assembly Triggered by Cis – Trans Polyproline Isomerization

Abstract Polyproline exists in two forms, the all-cis right-handed polyproline helix (type I) and the all-trans left-handed polyproline helix (type II). While the former is favored in common organic solvents, the latter is favored in aqueous solutions. Taking advantage of the hydrophilicity of type II polyproline, we prepared peptide-based nanostructures from a series of block copolymers of ε-caprolactone and l-proline. Copolymers were synthesized via N-carboxyanhydride polymerization in DMF using amino-ended polycaprolactone as initiator and covering a broad range of polyproline compositions. By simple stirring in water, the cis–trans isomerization of polyproline triggered their solubilization, leading to the spontaneous self-assembly of the copolymers into colloidally stable nanoparticles. Optical rotation measurements demonstrated the mutarotation of prolyl residues and circular dichroism spectroscopy shed light on the preferential type II secondary structure of polyproline that stabilizes nanostructures. Nanodevices encapsulated doxorubicin hydrochloride, highlighting their potential as drug delivery systems.