Research

Metallic nanoparticles for multimodal cancer therapy

TEM image of Au-Fe3O4 nanoheterodimers
Au-Fe3O4 nanoheterodimers
TEM image of mesoporous silica nanoparticles
mesoporous silica nanoparticles

1. Synthesis and characterization of

  • silicon quantum dots
  • iron-doped silicon NPs
  • magnetic mesoporous silica NPs
  • ferrite NPs
  • noble metal – Fe3O4 nanoheterodimers

 

2. Multimodal cancer therapy

These synthesized NPs act as X-ray dose enhancers in radio-therapy by increasing the reactive oxygen species (ROS) production.

The heterogenity of tumor tissues and the resistance of cancer cells towards monotherapies indicate the necessity to combine two or more forms of cancer treatment.

For example: Combination of radio-therapy with

  • chemo-therapy,
  • gene-therapy,
  • hypoxia treatment

whereat these nanoparticles were additionally used for the delivery of

  • anticancer drugs,
  • inhibitors,
  • NO donors,
  • siRNA.

Image shows the simultaneous generation of hydroxyl radicals and peroxynitrite at the surface of NOBF4 functionalized nanoheterodimers
Simultaneous production of ROS and RNS at the surface of NOBF4 functionalized nanoheterodimers

Image shows the difference in cell survival of brast cancer and breast epithelial cells. The higher concentration of hydroxyl radicals combined with a higher concentration of SPIONs inside the cancer cells enhanced the hydroxyl radical formation after X-ray radiation. Therefore a higher number of cancer cells die.
The combination of high intracellular SPION and H2O2 concentration leads to a drastically increased production of highly toxic hydroxyl radical after X-ray radiation. => Death of cancer cells

 

3.  Applications

TEM shows the cellular uptake of ferrite nanoparticles
TEM image of a MCF-7 cell with ferrite nanoparticles

3.1 2D cell cultures

The influence of NPs on cellular and molecular level is examined via 2D cell culture studies e. g. on breast, lung and colon cancer cell lines and non-tumorogenic breast or umbilical endothelial cells.

For example studies on

  • biocompatibility
  • cellular uptake
  • ROS production
  • activity of ROS detoxifying enzymes
  • cell death

 

3.2 3D tumor spheroids

3D cell culture  are excellent models for metastases by mimicking

  • 3D cellular interactions
  • an extracellular matrix
  • diffusion limits of oxygen and nutrients
  • pH, metabolic and proliferative gradients

Treatment: Caffeic acid Au-Fe3O4 nanoheterodimers, X-rays (5 doses of 2 Gy)

Tumor spheroid

 Healthy spheroid
Day 1
Day 7