Aug 13, 2014
Nanoparticles tackle cancer with heat and 'suicide genes'
Gene therapy can offer an effective treatment for drug-resistant radio-insensitive cancer. However, progress has been hampered by the difficulties in developing an appropriate delivery mechanism. Now researchers have demonstrated for the first time that magnetic nanoparticles provide safe, effective and targeted "suicide-gene" delivery to cells of a particularly prevalent and highly resilient type of liver cancer. Because the nanoparticles are magnetic they can also be used for hyperthermia treatments, where magnetic energy is converted into heat to elevate the temperature of the surrounding cancerous tissue, increasing the overall therapeutic effect of the gene therapy.
"Our in vivo and in vitro experiments showed that the gene therapy combined with the heating treatment was very effective," explains Chenyan Yuan, a researcher from Southeast University in China. "In mice, we saw that the tumour growth rate, volume and mass were significantly less in the combined treatment group compared to gene therapy and hyperthermia therapy alone."
Yuan and colleagues from the Affiliated Zhong Da Hospital of Southeast University and Jiangsu Key Laboratory for Biomaterials and Devices in China equipped the magnetic nanoparticles with a tumour-specific promoter gene to specifically tackle hepatocellular carcinoma, which is the most common form of liver cancer and causes more than 600,000 deaths worldwide each year. The promoter gene could be easily replaced to track down and treat other cancers in the body.
The devil's in the delivery
For several years, gene therapy has been acknowledged as a promising candidate to treat a wide range of diseases and genetic disorders. The concept of gene therapy is fairly straightforward, tackling disease at the DNA level by replacing defective, disease-causing genes with healthy genes, but it has proved to be very difficult in practice, with one of the main issues being the choice of a suitable vehicle, or vector, to transport and introduce healthy genes into cells.
Scientists have traditionally used genetically engineered viruses as a vector because they are naturally programmed to insert their DNA into a foreign cell. However, the viruses have been known to randomly integrate themselves onto chromosomes and also provoke an immune response in the host, causing major complications. As a result, scientists have proposed using functional nanoparticles as a vector to avoid these issues and enhance the therapeutic effect of the delivered genes.
As Yuan points out, "magnetic nanoparticles have proven to be an extremely effective alternative to traditionally used vectors. They are very efficient when it comes to delivering DNA into a cell and do not provoke an immune response in the host. They are also safe, simple to use and easy to produce on a large scale."
In their study, the researchers fabricated iron-oxide magnetic nanoparticles, which were around 20–30 nm wide and coated them with a positive charge so that the negatively charged DNA molecules could bind strongly to them.
The DNA that they attached to the magnetic nanoparticles included the "suicide gene", which stops the cells in the tissue proliferating and promotes cell death, as well as a tumour-specific "promoter" gene that acts as the driver of the vehicle, directing the magnetic nanoparticle to the specific tissue.
The magnetic nanoparticles were assessed to see how well the different genes combined, and then tested in vitro on human liver cancer cells and in vivo on healthy female mice. During the tests, the magnetic nanoparticles were exposed to magnetic energy through an alternating magnetic field, which they were able to convert into heat, raising the temperature of the surrounding cancerous tissue to 42–44 °C.
"Our results showed that the magnetic nanoparticles could elevate the temperature of the selected tissue into an effective therapeutic range, and avoid unwanted cell death and heating to normal tissues," says Yuan.
Full details are reported in Nanotechnology.
About the author
Michael Bishop works at IOP Publishing.