Polyplex micelles (PMs) prepared from pDNA and block copolymer containing a nonionic hydrophilic segment and a polycation segment through electrostatic interaction is a promising carrier system for non-viral gene delivery. The PMs structure add stealthiness to pDNA in a physiological environment owing to hydrophilic shell. Nevertheless, the harsh environment of in vivo condition limits the practical use of PMs. Among various obstacles, polyanionic compounds that can cause disassembly of PMs by polyanion exchange and abundant nucleases are committing major interfering obstacles. To improve the stability of PMs against them, we demonstrated here the PMs with the hydrophobic protective palisade. The novel triblock copolymer composed of hydrophilic and biocompatible poly(2-ethyl-2-oxazoline) (PEtOx) segment, thermoresponsive poly(2-n-propyl-2-oxazoline) (PnPrOx) segment, and DNA binding cationic poly(Lysine) (PLys) segment was designed. The triblock copolymer allowed for obtaining PMs integrating with the protective palisade between hydrophilic outer shell compartment and condensed pDNA core compartment by preparing PMs at 4 �C and subsequent incubation at 37 �C, which is above the LCST of PnPrOx segment  . With this thermal treatment, the hydrophobized PnPrOx segment successfully settled on the interface of the core, providing the tolerability against DNase I attack as well as dissociation triggered by polyanion. Eventually, the PMs demonstrated promoted cellular uptake and thereby increased transfection efficiency, as well as improved blood circulation property, and the appeal of the design concept of thermo-stimulated PMs as smart gene carrier.

Design of poly(oxazoline) based triblock copolymer for polyplex micelles with core protective parisade

248th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.