Multicomponent Polymerization Toward Cationic Polymers For Efficient Gene Delivery

Gene therapy has become a promising technique for the treatment or prevention of espoused and genetic diseases.Currently,major somatic gene transfer techniques use either viral or non-viral gene delivery vectors.Viral vectors exhibit high gene transfer efficiency,but are incomplete in quite a lot of areas,including the induction of a host inflammatory and immune response.Some of these problems can be avoided by employing non-viral vehicles,such as cationic polymers or liposomes.The complexes which they form with DNA are regarded as “lipoplexes” or “polyplexes,respectively,and make up the most auspicious alternative to the use of viral vectors for gene therapy.Here,a new class of cationic polymers containing tertiary amine,thioether,and hydroxyl groups were prepared via a catalyst-free,multicomponent polymerization method using dithiol,formaldehyde,and di-sec-amine with a ratio of 1:2:1,to access a library of water-soluble polymers with well-defined structures and suitable molecular weights(Mw ranging from 5000 Da to 8000Da)in high yields(up to 90%).Such polycations have been demonstrated to be promising non-viral gene delivery vectors with high transfection efficiency(up to 3.5-fold of PEI25k)and low toxicity with multiple functionalities:(1)efficient gene condensation by tertiary amine groups;(2)reactive oxygen species(ROS)scavenging by thioether groups;(3)positive charge shielding by hydroxyl groups.Both the thioether and hydroxyl groups contributed to reduce the cytotoxicity of the polycations by tuning the oxidative stress and preventing the undesired serum binding.The optimized polycations could achieve high transfection efficiency under the serum conditions,indicating the great potential as a non-viral gene delivery vector candidate for clinical application.