'Death switch' in cancer cells can be flicked by remote controlled nanoparticles


A magnetic field activates the nanoparticles flicking the cells' 'death switch', altering zebrafish embryo development

Nanoparticles can be used as a remote-controlled magnetic death switch to kill cancer cells, according to researchers from Korea.1Jeon-Soo Shin and Jinwoo Cheon of Yonsei University, in Seoul, and their colleagues have hooked up zinc-doped iron oxide magnetic nanoparticles to an antibody that targets a receptor on colon cancer cells. When ‘activated’ by an external magnetic field, the antibody targets DR4, the cancer cells' death receptor and triggers programmed cell death, apoptosis.

Cheon and colleagues explain how nanoparticles offer the possibility of controlling cell signalling pathways. Cell signalling allows cells to exchange information and underpins differentiation, growth, metabolism and many the processes. It also allows cells to trigger apoptosis to ensure that tissues do not grow out of control nor cells malfunction.

The team's approach focuses on a recently discovered extrinsic apoptosis signalling pathway involving death receptors present on the surface of cells, which has become an important spur for the development of novel cancer drugs. Such efforts have investigated biochemical ligands that can attach to these death receptors. Unfortunately, these ligands have only a very short half-life in blood plasma and so much of any administered ligand will degrade quickly before it can even reach the receptors. The Korean team therefore turned to nanotechnology and the ease with which a more biological, as opposed to biochemical, trigger for the death receptors might be transported to cancer cells effectively.

The team realised that adding a magnetic element might allow them to control the necessary signalling process remotely and non-invasively using a magnetic field. This would allow them to control the position of magnetic nanoparticles in the body and so target specific malignant tissues. The team has demonstrated proof of principle using zebrafish and demonstrated that they can operate the magnetic death switch on the micrometre scale.

‘It's an interesting article,’ Arnd Pralle of Buffalo University, New York, says. ‘It uses a method demonstrated first by Mannix2 and improves the nanoparticles and field geometry.’ He points out that this combination allowed the researchers to do in vivo experiments. ‘This new study is more an incremental improvement of that method than anything revolutionary,’ he adds. ‘It really does not overcome the main limitation that it works only in a small range of field gradient which covers a small space.’

Shin, however, points out that this is the first demonstration of in vivo feasibility of a magnetic nano-switch system. ‘Recent studies only focused on in vitro systems due to the biological complexity of live animals,’ he says. ‘Our study is one of the breakthroughs providing an effective way of cell function control in live vertebrates in a precise spatio-temporally regulated manner.’ He adds that the research specifically investigated how the apoptosis signalling pathway involved in cancer and other diseases might be manipulated clinically.