Quaternized starch-based carrier for siRNA delivery: From cellular uptake to gene silencing

Eliz Amar-Lewis, Aharon Azagury, Ramesh Chintakunta, Riki Goldbart, Tamar Traitel, Jackson Prestwood, Dalit Landesman-Milo, Dan Peer, Joseph Kost

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


RNAi therapeutics is a powerful tool for treating diseases by sequence-specific targeting of genes using siRNA. Since its discovery, the need for a safe and efficient delivery system for siRNA has increased. Here, we have developed and characterized a delivery platform for siRNA based on the natural polysaccharide starch in an attempt to address unresolved delivery challenges of RNAi. Modified potato starch (Q-starch) was successfully obtained by substitution with quaternary reagent, providing Q-starch with cationic properties. The results indicate that Q-starch was able to bind siRNA by self-assembly formation of complexes. For efficient and potent gene silencing we monitored the physical characteristics of the formed nanoparticles at increasing N/P molar ratios. The minimum ratio for complete entrapment of siRNA was 2. The resulting complexes, which were characterized by a small diameter (~ 30 nm) and positive surface charge, were able to protect siRNA from enzymatic degradation. Q-starch/siRNA complexes efficiently induced P-glycoprotein (P-gp) gene silencing in the human ovarian adenocarcinoma cell line, NCI-ADR/Res (NAR), over expressing the targeted gene and presenting low toxicity. Additionally, Q-starch-based complexes showed high cellular uptake during a 24-hour study, which also suggested that intracellular siRNA delivery barriers governed the kinetics of siRNA transfection. In this study, we have devised a promising siRNA delivery vector based on a starch derivative for efficient and safe RNAi application.

Original languageEnglish (US)
Pages (from-to)109-120
Number of pages12
JournalJournal of Controlled Release
Issue number1
StatePublished - Jul 10 2014


  • Drug delivery
  • Polysaccharide
  • Quaternized starch
  • Self-assembly complexes
  • Small interfering RNA

ASJC Scopus subject areas

  • Pharmaceutical Science


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