It is currently believed that magnetic nanoparticle heaters (MNHs) can kill cancer cells only when the temperature is raised above 43 °C due to energy dissipation in an alternating magnetic field. On the other hand, simple heat conduction arguments indicate that in small tumors or single cells the relative rates of energy dissipation and heat conduction result in a negligible temperature rise, thus limiting the potential of MNHs in treating small tumors and metastatic cancer. Here we demonstrate that internalized MNHs conjugated to epidermal growth factor (EGF) and which target the epidermal growth factor receptor (EGFR) do result in a significant (up to 99.9%) reduction in cell viability and clonogenic survival in a thermal heat dose dependent manner, without the need for a perceptible temperature rise. The effect appears to be cell type specific and indicates that magnetic nanoparticles in alternating magnetic fields may effectively kill cancer cells under conditions previously considered as not possible.

Summary There are two main mechanisms by which cells become multidrug resistant (MDR): by increasing drug efflux pumps on the cell membrane and by increasing anti-apoptotic pathways. The use of nanotechnology to develop nanodelivery systems has allowed researchers to overcome limitations of antineoplastic drugs by increasing the solubility of the drug and decreasing the toxicity to healthy tissues. By encapsulating drugs into nanoparticles that bypass the efflux pumps, drug efflux is reduced, hence increasing the intracellular concentration of the drug. siRNA has the ability to disrupt cellular pathways by knocking down genes, opening the door to down regulating anti-apoptotic pathways. The use of nanocarriers to deliver siRNA, prevents both renal clearance and RNase degradation by protecting siRNA chains, increasing their half life in blood. It has been suggested that co-delivering drugs and siRNA together in the same delivery system would be more effective in overcoming resistance of cancer cells than co-treatment of cancer cells with delivery systems carrying either siRNA or drugs. In this study we discuss the progress of nanoscale co-delivery systems in overcoming multidrug cancer resistance.

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