Faculty of Science REF Fund 2011/12 Tranche 2
Synthesis of magnetic nanoparticles as drug delivery systems for the
treatment of drug-resistant cancer cells
Prof. Martin Michaelis, Dr. Serena Corr, Prof. Mark Smales
Different types of nanoparticles are under intensive investigation as carrier systems
for anti-cancer drugs. They modify the cellular uptake and accumulate in tumours due
to the “Enhanced Permeability and Retention” (EPR) effect that is apparently a
consequence of an enhanced permeability of the tumour vasculature and a lack of an
effective lymph drainage. Here, we investigated the properties of magnetic
nanoparticles that are prepared using microwave-assisted methods in Serena Corr’s
lab. They are composed of magnetic iron oxide cores and coated with a
polyelectrolyte shell. These nanocomposites have previously shown good potential
as contrast agents for magnetic resonance (MR) imaging.
Goals:
- Investigation of the cytotoxicity/tolerability of magnetic nanoparticles
- Investigation of the cellular uptake of magnetic nanoparticles
Results:
The project was performed successfully. Different nanoparticle preparations were
tested for their effects on the viability of cancer (UKF-NB-3 neuroblastoma) and
primary human cells (human foreskin fibroblasts, retinal pigment epithelial cells).
Initially, some preparations exerted cytotoxic effects in cell cultures. However, we
could show that the tolerability of the investigated magnetic nanoparticles depends
on the purification procedures after their synthesis. When an optimised purification
protocol was applied, the nanoparticles were well tolerated in the tested
concentrations. This showed that toxicities probably arose from intermediates
resulting from the nanoparticle production process. The purified nanoparticles were
found to be well tolerated by the investigated cell types.
Moreover, the investigated magnetic nanoparticles were labelled with the
fluorescence dye rhodamin in order to study the nanoparticle uptake into cancer
cells. Results revealed that non-toxic concentrations of the magnetic nanoparticles
developed by Serena Corr’s group are readily internalised by UKF-NB-3
neuroblastoma cells.
The results will be included in a common manuscript by the applicants. This
manuscript will describe the preparation and biological testing of the magnetic
nanoparticles. The submission of the publication is planned for October 2012.