Synthesis and characterization of bioreducible cationic biarm polymer for efficient gene delivery.

We synthesized a new cationic AB2 miktoarm block copolymer consisting of one poly (ethylene glycol) (PEG) block and two cationic poly (l-lysine) (PLL) blocks, wherein the PLL blocks were conjugated to the PEG blocks with or without a bioreducible linker (disulfide bonds). Bioreducible and non-bioreducible miktoarm block copolymers (mPEG-(ss-PLL)2 and mPEG-PLL2 ) were prepared for efficient gene delivery as a non-viral gene delivery approach. Both cationic copolymers (bioreducible and nonbioreducible) efficiently formed the nanopolyplexes with plasmid DNA (pDNA) through electrostatic interaction at different weight ratio of polymer and pDNA. Gene condensation ability of the polymers and release of the DNA under reduction condition were measured by gel electrophoresis. Dynamic light scattering (DLS) and field-emission transmission electron microscopy (FE-TEM) were used to measure the average hydrodynamic diameter and morphology of the nanoparticles, respectively. The bioreducible nanopolyplexes showed lower cytotoxicity and higher gene expression than the non-reducible nanopolyplexes in cancer cells.