Glutathione-mediated shedding of PEG layers based on disulfide-linked catiomers for DNA delivery

Abstract

Engineered PEG-detachable catiomers were developed as non-viral gene vectors to detach the PEG layers responsive to the intracellular reducing environment. These catiomers were found to exhibit high DNA binding ability and reduced cytotoxicity, as evidenced in agarose gel electrophoresis and MTT assays. The size of the mPEG-SS-PLL/DNA complexes was around 100 nm with a regular spherical shape, as observed under transmission electron microscopy (TEM). The complexes were stably dispersed in an aqueous medium with 10% serum. However, fast aggregation was observed in the presence of 10 mM glutathione (GSH) due to detachment of the PEG segment via disulfide cleavage. These complexes showed high transfection efficiency in 293T and Hela cells under optimized conditions. The experimental results indicated that the mPEG-SS-PLL catiomers may have promising potential as a non-viral gene vector.