Cisplatin drug delivery using gold-coated iron oxide nanoparticles for enhanced tumour targeting with external magnetic fields

The platinum-based chemotherapeutic drug cisplatin is highly effective in the treatment of solid tumours, but its use is restricted by poor bioavailability, severe dose-limiting side effects and rapid development of drug resistance. In light of this we have tethered the active component of cisplatin to gold-coated iron oxide nanoparticles to improve its delivery to tumours and increase its efficacy. Iron oxide nanoparticles (FeNPs) were synthesised via a co-precipitation method before gold was reduced onto the surface (Au@FeNPs). Aquated cisplatin was used to attach {Pt(NH3)(2)} to the nanoparticles by a thiolated polyethylene glycol linker forming the desired product (Pt@Au@FeNP). The nanoparticles were characterised by dynamic light scattering, scanning transmission electron microscopy, UV-Vis spectrophotometry, inductively coupled plasma mass spectrometry and electron probe microanalysis. The nanoparticles increase in size as they are constructed, with the synthesised FeNPs having a diameter of 5-50 nm, which increases to 20-80 nm for the Au@FeNPs, and to 60-120 nm for the Pt@Au@FeNPs. Nanoparticle drug loading was found to be 7.9 x 10(-4) moles of platinum per gram of gold. The FeNPs appear to have little inherent cytotoxicity, whereas the Au@FeNPs are as active as cisplatin in the A2780 and A2780/cp70 cancer cell lines. More importantly the Pt@Au@FeNPs are up to 110-fold more cytotoxic than cisplatin. Finally, external magnets were used to demonstrate that the nanoparticles could be accumulated in specific regions and that cell growth inhibition was localised to those areas. (C) 2012 Elsevier B.V. All rights reserved.