Redox-triggered intracellular siRNA delivery.

Gene silencing using small interfering RNA (siRNA) is a promising strategy for the treatment of multiple diseases. However, the low in vivo stability of siRNA, its poor pharmacokinetics and inability to penetrate inside cells limit its employment in the clinic. Here, we present a novel redox-sensitive micellar nanopreparation based on a triple conjugate of polyethylene glycol, polyethyleneimine and phosphatidylethanolamine, PEG-SS-PEI-PE (PSSPD). This non-toxic system efficiently condenses siRNA and specifically downregulates target green fluorescent protein (GFP) only under reducing conditions via intracellular siRNA release after de-shielding of PEG due to increased glutathione (GSH) levels characteristic of cancer cells.