Friday April 18 2008
Cancer cells under the microscope
“Magnets can guide anti-cancer drugs to tumours” reported The Guardian today. They go on to discuss research on a new drug delivery method that suggests that cancer treatments can be delivered straight to tumour cells using tiny magnets. This, the paper said, will save healthy cells from the toxic effects of these drugs.
At present, the use of this technology in man is speculative and further research is required. The study will be of interest to the scientific community and represents a step forward in the search for ways of treating cancer that are more targeted and therefore less toxic for patients.
Where did the story come from?
Dr M Muthana and colleagues from the University of Sheffield Medical School, the University of Kent, and Keele University School of Medicine carried out the research. The study was funded by the Biotechnology and Biological Sciences Research Council. The study was published in the peer-reviewed medical journal: Gene Therapy.
What kind of scientific study was this?
In this laboratory study, the researchers used models and live mice to explore a new method of delivering therapeutic genes to diseased tissues such as tumours.
The researchers were particularly interested in developing a technology that takes advantage of the properties of cells called monocytes. Monocytes, a type of white blood cell, can migrate from the blood into body tissues. Here, they become macrophages, which operate as part of the immune system by taking up foreign matter and helping to destroy bacteria, protozoa and tumour cells. Monocytes are known to enter malignant tumours in large numbers, becoming macrophages, and to accumulate in areas of tumours where there is no blood supply (the most inaccessible parts of tumours). This property makes them potential vehicles to deliver therapy deep within tumours.
Magnetic nanoparticles (MNPs) have been bound to chemotherapy drugs in the past and a magnetic field used to direct and concentrate the drug in the target tissue. Though there is some success with this approach, relatively little of the drug is able to penetrate tumours beyond their surface tissues. The researchers were exploring whether monocytes loaded with magnetic nanoparticles could be attracted to tumour cells using a magnetic field.
There were a number of different parts to the experiment. To begin with, the researchers cultured monocytes with magnetic nanoparticles to see whether they would take them up (absorb them). They then determined whether these “magnetic” monocytes would be attracted to a magnetic field.
To see whether these magnetised monocytes would still be able to penetrate into tumours, the researchers set up an experimental model. The model was set up in a chamber, at the bottom of which were “tumour spheroids” (balls of human tumour cells). The middle of the chamber constituted a layer of endothelial cells (the type of cells that line the interior of blood vessels) and the upper part of the chamber contained the magnetic monocytes. A magnet was then applied to the bottom of the chamber. The researchers were interested in whether the magnet would attract more cells to the tumours and how the monocytes behaved when they were genetically modified to carry a gene.
The researchers repeated their experiments in live mice injected with human prostate cancer cells that had grown tumours on their legs. The mice were injected with monocytes loaded with magnetic nanoparticles and a marker gene that would later indicate where the monocytes had penetrated. A magnet was applied near the tumour site. When the mice were dissected, the researchers assessed the concentration of magnetic monocytes in their tumours and other tissues, and compared these concentrations to what happened when a magnet was not applied or when the mice were injected with normal (i.e. non-magnetic) monocytes.
What were the results of the study?
The researchers found that the monocytes quickly and effectively absorbed the magnetic nanoparticles and were not negatively affected by them.
In the experimental model, the monocytes containing the magnetic nanoparticles were attracted to the magnetic field, and they concentrated towards the side of the culturing vessel to which a magnet was being held. The monocytes were able to cross the endothelial layer in the model and penetrate the tumour spheroids, suggesting that being magnetised did not affect this ability of the cells. Applying a magnet to the bottom of the chamber near the tumour-like balls increased the infiltration of the monocytes into the tumours.
The use of the magnet significantly increased the amount of monocytes penetrating the mouse tumours and large numbers of these were detected in the deep parts of the tumour (that have little circulation and are usually hard to target with drugs).
What interpretations did the researchers draw from these results?
The researchers conclude that they have described a new “magnetic” approach to enhancing the uptake of genetically modified cells by the target tissue.
They say that their new technology could be used to overcome the problem of “poor uptake of cell-based forms of gene therapy by diseased tissues like malignant tumours”.
What does the NHS Knowledge Service make of this study?
This study in mice will be of interest to the scientific community as it represents a potential new use for magnetic nanoparticles, i.e. to help deliver gene therapies to diseased tissues. However, until the findings are repeated in humans, it is difficult to say how relevant and how imminent such treatments may be.
The researchers say that the technology “could markedly improve the efficacy of cell-based gene delivery protocols”. The fact that human tumour cells were used may increase the relevance of the study’s findings and the chances of a practical application, but more will need to be done to see whether human monocytes behave in a similar way in the human body. As it stands, treatments using this method are a long way off.
The potential of this technology should not be underestimated and will no doubt be the subject of future research. The findings represent a step forward in the search for better, more targeted and therefore less toxic treatments for human cancers.