Single-walled carbon nanotubes functionalized with aptamer and piperazine-polyethylenimine derivative for targeted siRNA delivery into breast cancer cells

Int J Pharm. 2015 May 15;485(1-2):50-60. doi: 10.1016/j.ijpharm.2015.02.031. Epub 2015 Feb 21.

Abstract

Epithelial cell adhesion molecule (EpCAM) is a glycosylated type 1 membrane protein which is frequently over expressed in most solid tumors and it has recently been identified as a cancer stem cell (CSC) marker. Specific targeting of CSCs using nano-carriers would enhance treatment efficacy of cancer. In this study, we used a RNA aptamer against EpCAM (EpDT3) attached physically to our newly synthesized non-viral vector, based on single-walled carbon nanotube (SWNT) conjugated to piperazine-polyethylenimine derivative. The DNA transfection efficiency and siRNA delivery activity of the synthesized vector was investigated against upregulated BCL9l, which has been associated with breast and colorectal cancers. The complexes of the vector-aptamer/siRNA could specifically induce apoptosis by more than 20% in MCF-7 cell line as a positive EpCAM than MDA-MB-231 cells which are EpCAM negative. The decrease of BCL9l protein level was observed with western blot analysis in MCF-7 cells indicating the targeted silencing activity of the complex.

Keywords: Aptamer; Epithelial cell adhesion molecule; Gene delivery; Single-walled carbon nanotube; siRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / genetics*
  • Antigens, Neoplasm / metabolism
  • Apoptosis
  • Aptamers, Nucleotide / chemistry
  • Aptamers, Nucleotide / genetics
  • Aptamers, Nucleotide / metabolism*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / therapy*
  • Cell Adhesion Molecules / genetics*
  • Cell Adhesion Molecules / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Epithelial Cell Adhesion Molecule
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MCF-7 Cells
  • Nanomedicine
  • Nanotubes, Carbon / chemistry*
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Piperazines / chemistry*
  • Polyethyleneimine / chemistry*
  • RNA, Small Interfering / genetics*
  • RNA, Small Interfering / metabolism
  • RNAi Therapeutics / methods*
  • Time Factors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transfection / methods*

Substances

  • Antigens, Neoplasm
  • Aptamers, Nucleotide
  • BCL9L protein, human
  • Cell Adhesion Molecules
  • DNA-Binding Proteins
  • EPCAM protein, human
  • Epithelial Cell Adhesion Molecule
  • Nanotubes, Carbon
  • Piperazines
  • RNA, Small Interfering
  • Transcription Factors
  • Polyethyleneimine