Functional modification of amide-crosslinked oligoethylenimine for improved siRNA delivery

Succinylation of OEI-HD-1 at 12% of nitrogens strongly reduced siRNA binding and silencing activity. All other OEI-HD-1 derivates displayed improved in vitro biocompatibility and siRNA mediated luciferase gene knockdown in Neuro2A/eGFPLuc cells. Succinylation at 7% of nitrogens strongly reduced cytotoxicity of the polymer and extended the functional window between gene silencing and cytotoxicity. Incorporation of DMMAn-Mel and PEG into OEI-HD-1 generated a pH-responsive lytic polymer conjugate with the highest potency in siRNA mediated gene knockdown and largest functional activity/biocompatibility window.