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, we have developed a series of novel cationic
polyrotaxanes consisting of multiple oligoethyleneimine-grafted
beta-cyclodextrin rings threaded on a poly(
ethylene glycol)-poly(
propylene glycol)-poly(
ethylene glycol) triblock copolymer chain. In this study, these cationic
polyrotaxanes with different oligoethyleneimine chain lengths were investigated for
DNA binding ability, cytotoxicity, and gene transfection efficiency in
cancer cells. Fluorescent titration assay results indicated that all the
polyrotaxanes could completely condense plasmid
DNA and form stable complexes at N/P ratio of 2, where the N/P ratio is the molar ration of
amine groups in the cationic molecule to
phosphate groups in the
DNA. Particularly, tapping mode AFM imaging in aqueous environment was conducted to observe the morphology of the
polyrotaxane/
DNA complexes and their formation processes in real time. In both SK-OV-3 and PC3
cancer cells, these
polyrotaxanes showed low cytotoxicity and high transfection efficiency which is comparable to or significantly higher than that of high molecular weight branched
polyethylenimine (25 kDa), one of the most effective gene-delivery
polymers studied to date. In addition, the synthesized
polyrotaxanes displayed sustained gene delivery capability in PC3 cells in the presence or absence of serum. Therefore, these cationic
polyrotaxanes with strong
DNA binding ability, low cytotoxicity, and high and sustained gene delivery capability have a high potential as novel nonviral gene carriers in clinical cancer gene
therapy.