Cationic Polyrotaxanes as a Feasible Framework for the Intracellular Delivery and Sustainable Activity of Anionic Enzymes: A Comparison Study with Methacrylate-Based Polycations.

We have developed cationic polyrotaxanes composed of N,N-dimethylaminoethyl (DMAE) group-modified α-cyclodextrins (α-CDs) threaded along a poly(ethylene glycol) (PEG) chain capped with a terminal bulky stopper (DMAE-PRX) for the intracellular delivery of proteins through the polyelectrolyte complexation. Herein, to ascertain the effect of supramolecular backbone structure of cationic polyrotaxanes, the physicochemical properties and biological activity of polyelectrolyte complex with anionic β-galactosidase (β-gal) were investigated in comparison to a cationic linear polymer, poly[2-(N,N-dimethylaminoethyl) methacrylate] (PDMAEMA). In the cellular experiments, the DMAE-PRX/β-gal complexes exhibited higher intracellular uptake of β-gal and sustainable enzymatic activity of delivered β-gal than the PDMAEMA/β-gal complexes. It is considered that the cationic polyrotaxanes are promising supramolecular backbone structure for the intracellular protein delivery.