Evaluation of dendrimer type bio-reducible polymer as a siRNA delivery carrier for cancer therapy

J Control Release. 2015 Jul 10:209:179-85. doi: 10.1016/j.jconrel.2015.04.039. Epub 2015 Apr 30.

Abstract

Small interfering ribonucleic acid (siRNA), 20-25 base pairs in length, can interfere with the expression of specific genes. Recently, many groups reported the therapeutic intervention of siRNA in various cancer cells. In this study, dendrimer type bio-reducible polymer (PAM-ABP) which was synthesized using arginine grafted bio-reducible poly(cystaminebisacrylamide-diaminohexane) (ABP) and polyamidoamine (PAMAM) was used to deliver anti-VEGF siRNA into cancer cell lines including human hepatocarcinoma (Huh-7), human lung adenocarcinoma (A549), and human fibrosarcoma (HT1080) cells and access their potential as a siRNA delivery carrier for cancer therapy. PAM-ABP and siRNA formed polyplexes with average diameter of 116 nm and charge of around +24.6 mV. The siRNA in the PAM-ABP/siRNA polyplex was released by 5mM DTT and heparin. VEGF gene silencing efficiency of PAM-ABP/siRNA polyplexes was shown to be more effective than PEI/siRNA polyplexes in three cell lines with the following order HT1080>A549>Huh-7.

Keywords: Bio-reducible polymer; Dendrimer; VEGF; siRNA.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dendrimers / administration & dosage*
  • Dendrimers / chemistry
  • Dendrimers / pharmacology
  • Gene Expression / drug effects
  • Humans
  • Neoplasms / therapy
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / chemistry
  • RNA, Small Interfering / pharmacology
  • Vascular Endothelial Growth Factor A / genetics*

Substances

  • Dendrimers
  • RNA, Small Interfering
  • Vascular Endothelial Growth Factor A