A supramolecular gene carrier composed of multiple cationic α-cyclodextrins threaded on a PPO–PEO–PPO triblock polymer

Cationic polymers have been studied as promising nonviral gene delivery vectors. In contrast to the conventional polycations with long sequences of covalently bonded repeating units, this work reports a supramolecular gene carrier where many cationic cyclic units are threaded over a polymer chain to form a chain-interlock structured gene carrier. A series of novel supramolecular cationic polyrotaxanes consisting of multiple α-cyclodextrin (α-CD) rings grafted with various linear or nonlinear oligoethylenimine (OEI) chains, which are threaded and capped over a reverse Pluronic poly(propylene oxide)–poly(ethylene oxide)–poly(propylene oxide) (PPO–PEO–PPO) amphiphilic triblock copolymer chain, were synthesized and characterized in term of their molecular and supramolecular structures, DNA binding and condensation ability, cytotoxicity, and in vitro gene transfection efficiency in cultured cells. The supramolecular cationic polyrotaxanes were found to contain 8 cationic α-CD rings that are threaded on a PPO–PEO–PPO triblock copolymer chain. They demonstrated strong ability to bind and condense plasmid DNA into nano-sized particles which are suitable for gene delivery. In both HEK293 and COS7 cells, these polyrotaxanes show low cytotoxicity and high transfection efficiency. In particular, the cationic polyrotaxanes displayed sustained gene delivery capability in HEK293 cells in both serum and serum free condition with the increasing expression duration.