Redox-triggered intracellular siRNA delivery

MUTLU AĞARDAN N. B. , Sarisozen C., Torchilin V. P.

CHEMICAL COMMUNICATIONS, vol.54, no.49, pp.6368-6371, 2018 (Peer-Reviewed Journal) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 54 Issue: 49
  • Publication Date: 2018
  • Doi Number: 10.1039/c8cc01376d
  • Journal Indexes: Science Citation Index Expanded, Scopus
  • Page Numbers: pp.6368-6371


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.