CpG oligodeoxynucleotide-loaded PAMAM dendrimer-coated magnetic nanoparticles promote apoptosis in breast cancer cells

Biomed Pharmacother. 2016 Mar;78:81-91. doi: 10.1016/j.biopha.2016.01.002. Epub 2016 Jan 19.

Abstract

One major application of nanotechnology in cancer treatment involves designing nanoparticles to deliver drugs, oligonucleotides, and genes to cancer cells. Nanoparticles should be engineered so that they could target and destroy tumor cells with minimal damage to healthy tissues. This research aims to develop an appropriate and efficient nanocarrier, having the ability of interacting with and delivering CpG-oligodeoxynucleotides (CpG-ODNs) to tumor cells. CpG-ODNs activate Toll-like receptor 9 (TLR9), which can generate a signal cascade for cell death. In our study, we utilized three-layer magnetic nanoparticles composed of a Fe3O4 magnetic core, an aminosilane (APTS) interlayer and a cationic poly(amidoamine) (PAMAM) dendrimer. This will be a novel targeted delivery system to enhance the accumulation of CpG-ODN molecules in tumor cells. The validation of CpG-ODN binding to DcMNPs was performed using agarose gel electrophoresis, UV-spectrophotometer, XPS analyses. Cytotoxicity of conjugates was assessed in MDA-MB231 and SKBR3 cancer cells based on cell viability by XTT assay and flow cytometric analysis. Our results indicated that the synthesized DcMNPs having high positive charges on their surface could attach to CpG-ODN molecules via electrostatic means. These nanoparticles with the average sizes of 40±10nm bind to CpG-ODN molecules efficiently and induce cell death in MDA-MB231 and SKBR3 tumor cells and could be considered a suitable targeted delivery system for CpG-ODN in biomedical applications. The magnetic core of these nanoparticles represents a promising option for selective drug targeting as they can be concentrated and held in position by means of an external magnetic field.

Keywords: Cancer therapy; CpG-ODN; Drug delivery; Flow cytometry; PAMAM dendrimer; Targeted therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dendrimers / chemical synthesis
  • Dendrimers / chemistry*
  • Drug Delivery Systems
  • Dynamic Light Scattering
  • Endocytosis / drug effects
  • Female
  • Flow Cytometry
  • Humans
  • Hydrodynamics
  • Inhibitory Concentration 50
  • Magnetite Nanoparticles / chemistry*
  • Oligodeoxyribonucleotides / pharmacology
  • Oligodeoxyribonucleotides / therapeutic use*
  • Particle Size
  • Photoelectron Spectroscopy
  • Static Electricity

Substances

  • CPG-oligonucleotide
  • Dendrimers
  • Magnetite Nanoparticles
  • Oligodeoxyribonucleotides
  • PAMAM Starburst